Responsável
Luiz Eduardo Atalécio

Esta seção tem por objetivo divulgar os resumos dos mais recentes artigos publicados na literatura mundial a respeito da epidemiologia, prevenção, diagnóstico, estadiamento, tratamento e prognóstico do câncer.

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Vegetables, fruit, and cancer prevention: A review
Kristi A., Steinmetz, PhD., R.D., John D. Potter M.D., PhD

In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented.

Pharmacologic treatment of cancer pain
Michael H. Levi, MD, PhD

Pain from cancer is a major health care problem1-3. Thirty percent of patients with cancer have pain at the time of diagnosis, and 65 to 85 percent have pain when their disease is advanced2, 4-6. The impact of cancer pain is magnified by the interaction of pain and its treatments with other common cancer symptoms: fatigue, weakness, dyspnea, nausea, constipation, and impaired cognition4, 6. Cancer pain can be effectively treated in 85 to 95 percent of patients with an integrated program of systemic, pharmacologic, and anticancer therapy7, 8. Many of the remaining patients can be helped by the appropriate use of invasive procedures9-11. In the final days of life, pain not controlled by therapies aimed at both comfort and function can be relieved by intentional sedation12-14. No patient with cancer needs to live or die with unrelieved pain.
There are three basic approaches to the control of pain: modifying the source of the pain, altering the central perception of pain, and blocking the transmission of the pain to the central nervous system15. The optimal use of these approaches in the control of cancer pain requires a thorough assessment of each patient's pain, cancer, concurrent medical problems, and psychosocial status16-18. An individualized plan of care must be established, implemented, re-assessed, and modified on a regular basis to maximize both the quality and duration of life. The pain of the vast majority of patients with cancer can be relieved through direct and indirect modification of the source of the pain combined with pharmacologic and nonpharmacologic alteration of the patients' perception of pain7, 8, 17, 18. This paper reviews the pharmacologic treatment of cancer pain in a guideline format to facilitate the translation of current knowledge into clinical practice (Table 1). Readers are referred to more extensive review articles16, 18, 19, guidelines17, 20, and textbooks9, 10, 21, 22 to integrate pharmacologic therapy with anticancer therapies, physical and psychosocial therapies, and procedural interventions to optimize patients' comfort and their ability to function.

Interleukin-2 therapy: A decade of slow but steady progress
Michael B. Atkins, MD, Boston, Massachusetts

In December 1985, Rosenberg and his colleagues at the Surgery Branch of the National Cancer Institute published the results of the first clinical trial involving high-dose recombinant interleukin-2 (IL-2)1. They reported tumor responses in 44% of cancer patients treated with high-dose IL-2 and autologous lymphokine-activated killer (LAK) cells. Responses were largely confined to patients with metastatic renal cell cancer (3 of 3) and melanoma (4 of 7). This publication propelled the field of cancer immunotherapy into the clinical realm. A decade into this often exhilarating, often frustrating journey, it is reasonable to take stock of the progress made and the obstacles that remain.
Clinical trials performed after the initial Surgery Branch publication revealed that the true response rate for high-dose IL-2/LAK cell therapy was in the 15% to 25% range for both renal cell carcinoma and melanoma2-4. Studies comparing IL-2 alone to IL-2/LAK cells indicated that, in contrast to the animal models, LAK cells added insignificantly to the antitumor effects of IL-2 in humans5, 6, thus enabling the elimination of this complex, labor intensive, and expensive component of the therapy. In 1992, the results of seven clinical trials involving 255 patients with metastatic renal cell cancer treated with a single high-dose IL-2 regimen were compiled for presentation to the U.S. Food and Drug Administration (FDA)7. This highly scrutinized database showed a response rate of 14%, with a 5% complete response rate and a median duration of response of 23.2 months. Over half of responding patients had tumor burdens in excess of 50 cm2 and over half of the patients exhibiting a partial response had a greater than 90% regression of measurable disease. The quality and durability of these responses led the FDA to approve high-dose IL-2 as the standard therapy for selected patients with metastatic renal cell carcinoma. Despite similar response rates, approval for IL-2 in metastatic melanoma has yet to be sought.

Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis
Italian Group for Antiemetic Research*
*See pages 809 and 810 for list of investigators and collaborating centres

Background: Differences in pharmacodynamic and pharmacokinetic characteristics among serotonin-receptor antagonists have been reported in preclinical studies. This prompted us to carry out a study to determine whether such differences are important in terms of clinical efficacy or tolerability.
Patients and methods: 973 consecutive cancer patients scheduled to receive cisplatin for the first time (at doses ³ 50 mg2), entered a double-blind multicenter randomized study comparing intravenous ondansetron 8 mg versus granisetron 3 mg. Dexamethasone 20 mg was added to both serotonin antagonists. On days 2 to 4 after chemotherapy all patients received oral metoclopramide plus intramuscular dexamethasone as antiemetic prophylaxis for delayed emesis. Nausea and vomiting were assessed daily until day 6 after chemotherapy.
Results: We evaluated 966 patients (483 receiving ondansetron and 483 granisetron). Complete protection from acute vomiting/nausea was obtained in 79.3%/72.0% of patients receiving ondansetron and in 79.9%/71.8% of those receiving granisetron. Complete protection from delayed vomiting/nausea was obtained in 69.7%/52.9% and 70.0%/49.6% of patients receiving the ondansetron or granisetron regimens, respectively. Adverse effects were mild and not significantly different between the two antiemetic regimens.
Conclusions: Ondansetron 8 mg and granisetron 3 mg, both combined with dexamethasone, showed similar efficacy and tolerability in the prevention of cisplatin-induced emesis. The choice between the two regimens can be dictated by their respective purchase prices.

Malignant cerebral glioma - I: Survival, disability, and morbidity after radiotherapy
Elizabeth Davies, Charles Clarke, Anthony Hopkins

Objective: To describe survival, disability, and morbidity after radiotherapy for malignant glioma.
Design: Two year prospective study with home interviews with patients and relatives.
Setting: Seven neurosurgical and radiotherapy centres in London.
Subjects: 105 patients aged 21 to 75: 59 had biopsy; 46 had partial macroscopic resection; 92 received radiotherapy; and 13 received steroids alone.
Main outcome measures: Survival, time free from disability, and changes in disability after treatment.
Results: Six and 12 month survival for radiotherapy patients was 70% and 39%, respectively. Age, World Health Organization clinical performance status, extent of surgery, and history of seizures before diagnosis each influenced survival. The Medical Research Council prognostic index was also significantly related to survival. Multivariate analysis showed that initial clinical performance status was the most important component of the index. Most (80%; 49/61) patients with a clinical performance status of 0, 1, or 2 lived at least six months before becoming permanently disabled. Most patients who had initially had a good clinical performance status (0-2) and who were alive six months after radiotherapy (68%; 36/52), however, had experienced either clinical deterioration or severe tiredness after treatment. In 17% (9/52) of these some permanent loss of function remained. These adverse effects were associated with increasing radiotherapy dose. Severely disabled patients (clinical performance status 3 or 4) gained little benefit.
Conclusion: Severely disabled patients gain little physical benefit from radiotherapy, whereas those not so disabled may experience considerable adverse effects.

Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases
Gabriel N. Hortobagyi, M.D., Richard L. Theriault D.O., Lester Porter, M.D., Douglas Blayney, MD, Allan Lipton, M.D., Clive Sinoff, M.D., Helen Wheeler, M.D., Joseph F. Simeone, M.D., John Seaman, PharmD, Robert D. Knight, M.D., Maika Heffernan, Ph.D., and Dirk J. Reitsma, M.D., for the Protocol 19 Aredia Breast Cancer Study Group*

Background: Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone.
Methods: Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or one surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial.
Results: The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pamidronate group than in the placebo group (13.1 vs. 7.0 months, P = 0.005), and the proportion of patients in whom any skeletal complication occurred was lower (43 percent vs. 56 percent, P = 0.008). There was significantly less increase in bone pain (P = 0.046) and deterioration of performance status (P = 0.027) in the pamidronate group than in the placebo group. Pamidronate was well tolerated.
Conclusions: Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases.

The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomised, controlled tamoxifen prevention study
J Chang, T.J. Powles, S.E. Ashley, R.K. Gregory, V.A. Tidy, J.G. Treleaven & R. Singh Breast Unit, Royal Marsden Hospital, Sutton, Surrey, UK

Background: The role of hormone replacement therapy (HRT) in women who have been treated for breast cancer remains controversial. The addition of tamoxifen may protect these women from any proliferative effect of exogenous oestrogen on the breast. The aim of this analysis was to determine if tamoxifen and HRT may be safely administered together.
Methods: We studied the interaction between HRT and tamoxifen on serum cholesterol, fibrinogen, antithrombin III (AT III) and bone mineral density (BMD) in postmenopausal healthy women enrolled in a randomised tamoxifen chemoprevention trial.
Results: Tamoxifen decreased serum cholesterol by a mean of 13% from pretreatment values (n = 153). The addition of HRT to tamoxifen did not result in further reduction in serum cholesterol (n = 20). HRT alone led to a reduction of serum cholesterol by a mean of 5% in 14 women on placebo. The addition of tamoxifen to HRT resulted in further reduction in serum cholesterol by a mean of 7% (n = 44). Significant reductions of plasma fibrinogen by 14% and AT III by 8% were seen in women who received tamoxifen. There were no further significant changes in these coagulation factors in women on tamoxifen/HRT combinations Tamoxifen resulted in an annual increase in BMD of the femur and spine by 2% and 1.5%, respectively, when compared to placebo (n = 38). The addition of HRT to tamoxifen resulted in further 2% annual increase in BMD of the femur.
Conclusions: We conclude that there were no significant adverse intereactions with tamoxifen and HRT in this small series of patients. The combination results in a reduction of serum cholesterol, increase in BMD especially in the femur and appears not to have any adverse effect on coagulation factors. Multicentre studies should be conducted to evaluate the effect of this combination on relieving menopausal symptoms, disease relapse and overal survival in women who have received treatment for breast cancer.

Meeting highlights: International consensus panel on the treatment of primary breast cancer
Aron Goldhirsch, William C. Wood, Hans-Jörg Senn, John H. Glick, Richard D. Gelber*

Breast cancer is a heterogeneous disease. The choice of primary treatments available today is based on features of the patient, the tumor, and the patient’s response to treatment. We have learned that the medical and social environments within which patients are being treated contribute to this heterogeneity with respect to the interpretation of available data on prognosis and cost-benefit of treatments. All of our knowledge about the selection of therapies is derived from results of case series and randomized clinical trials. Randomized clinical trials provide unbiased evidence of relative treatment efficacy on a selected patient population. A meta-analysis of randomized clinical trials is extremely effective in reducing statistical uncertainty.
In March 1992, the Consensus Panel of experts at the 4th International Conference on Adjuvant Therapy of Primary Breast Cancer held in St. Gallen, Switzerland, developed a series of guidelines and recommendations for the selection of treatments in several patient populations (1, 2). These guidelines and recommendations were based mainly on the syntheis of results from individual clinical trials and on the findings from the worldwide overview (3) that had been made public a few months before the conference was held. Since then, the proportion of women who are considered candidates for adjuvant therapy has shifted as a result of the statistically significant effects of chemotherapy, tamoxifen, and ovarian ablation identified in the worldwide overview.
During the past 3 years, several new concepts and treatment strategies have been studied. Some can be considered to assist in the treatment of patients today, while others are still undergoing clinical investigation to better define their usefulness. Table 1 describes some examples of these findings and their implications or status relative to patient care. These subjects were presented and discussed at the 5th International Conference on Adjuvant Therapy of Primary Breast Cancer held in St. Gallen, Switzerland, in March 1995. At the last session of this conference, a panel of experts discussed prognostic and predictive factors, treatments for ductal carcinoma in situ (DCIS) and small, screening-detected tumors, as well as controversial issues related to the adjuvant treatment of lymph node-negative and lymph node-positive breast cancers. In this commentary, we describe some areas of ongoing research and update the treatment recommendations presented 3 years ago.

Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the nishinihon cooperative study group of adjuvant chemoendocrine therapy for breast cancer (ACETBC) of Japan
T. Morimoto¹, M. Ogawa², K. Orita³, K. Sugimachi⁴, T. Toge⁵, K. Dohi⁶, Y. Nomura⁷, Y. Monden⁸ and N. Ogawa^9
1School of Medical Sciences, The University of Tokushima, Kutamoto-cho 3 Tokushima 220; ²The Second Department of Surgery, Kumamoto University Medical School, Kumamoto; ³The First Department of Surgery, Okayama University Medical School, Okayama; ⁴The Second Department of Surgery, Faculty of Medicine, KyuShu University, Fukuoka; ⁵The Department of Surgery, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Hiroshima; ⁶The Second Department of Surgery, Hiroshima University School of Medicine, Hiroshima; ⁷The Department of Breast Surgery, National Kyushu Cancer Center Hospital, Fukuoka; ⁸The Second Department of Surgery, School of Medicine, The University of Tokushima, Tokushima; and ⁹St Marianna University, Kanagawa, Japan

Between 1985 and 1988, the effect of using ftorafur (FT) or PSK (an immunotherapy agent) in combination with the conventional postoperative adjuvant therapy using mitomycin (MMC) plus tamoxifen (TAM) was assessed in stage II, oestrogen receptor-positive (ER+) breast cancer patients. Furthermore, in ER- breast cancer stage II patients, the effects of postoperative adjuvant therapy using MMC plus FT were compared with the effects of postoperative adjuvant therapy using MMC plus PSK. Patients had primary stage II breast cancer and had undergone total mastectomy plus axillary dissection or more radical surgery. On the day of surgery, MMC (13 mg/m2) was administered intravenously. Then, ER+ patients received one of three regimens of drug therapy, starting 2 weeks after surgery: regimen A (daily oral treatment with 20 mg of TAM), regimen B (daily oral treatment with 20 mg of TAM and 3 g of PSK). ER - patients received either regimen D (daily oral treatment with 600 mg of FT) or regimen E (daily oral treatment with 3 g of PSK), starting 2 weeks after surgery. Of the 540 ER+ patients registered, 525 were evaluated. The 5-year overall survival rate for ER+ patients was higher for patients who received regimen B (94.2%) than for those who received regimen A (86.9%) or regimen C (89.9%) or regimen C (89.9%)(P = 0.063). The 5-year relapse-free survival rate was higher for regimen B (88.9%) than for regimen A (78.6%) and regimen C (77.2%) (P = 0.010). Stratified analysis revealed better results with the FT-combined therapy in patients positive for lymph node metastasis and premenopausal patients. These results indicate the effectiveness of using FT in combination with TAM. Of the 376 ER- patients registered, 364 were evaluated. The 5-year overall and relapse-free survival rate for ER- patients did not differ significantly between patients who received regimen D and those who received regimen E.

Risk of new primaries after chemotherapy and/or tamoxifen treatment for early breast cancer
A. Rubagotti¹, A. Perrotta², Casella³ & F. Boccardo^4
1Chair of Medical Oncology, Biostatistics Unit, University of Genoa; ²Department of Experimental Oncology, ³Department of Environmental Epidemiology, ⁴Department of Medical Oncology II, National Institute for Cancer Research, Genoa, Italy.

Background: Both chemotherapy and tamoxifen are widely used either alone or in combination as adjuvant treatment following mastectomy. Despite the fact that both of them exhibit carcinogenic properties in experimental models, detailed reports on the incidence of new primaries following chemotherapy and/or tamoxifen in patients with early breast cancer are limited.
Purpose: To investigate the incidence of new primaries (including opposite breast tumors and skin cancers) in untreated patients and in patients treated with either tamoxifen or chemotherapy or with both modalities.
Patients and methods: A total of 1696 patients with early breast cancer, 1286 of whom were treated with either CMF-based adjuvant chemotherapy (n = 410), tamoxifen (n = 656) or with a combination of the two (n = 220) were considered for the present analysis. Patients were operated on between November 1983 and December 1991 and were followed up to June 1994. Detailed information about second malignancies were available for all patients.
Results: Overall, 53 new primaries, 19 of them opposite breast tumors, occurred in 53 patients. The actuarial cumulative incidence rates at 5 years were: 3.1% (95% CI: 1.4% - 4.8%) in untreated patients; 1.7% (95% CI: 0.0% - 3.5%) in tamoxifen-treated patients; 4.2% (95% CI: 1.3% - 7.1%) in chemotherapy-treated patients and 2.6% (95% CI: 0.0% - 5.2%) in the chemo-tamoxifen group (all groups: P = n.s.; chemotherapy-treated versus tamoxifen-treated: P = 0.01). The corresponding figures, after exclusion of the patients with opposite-breast and skin tumors, were: untreated patients: 2% (95% CI: 0.6% - 3.4%); tamoxifen-treated patients: 0.95% (95% CI: 0.0% - 2.4%); chemotherapy-treated patients: 2.6% (95% CI: 0.4% - 4.8%); chemotherapy plus tamoxifen: 1.65% (95% CI: 0.4% - 3.8%); (all groups: P = n.s.; CT versus TAM P = 0.05). Chemotherapy-treated patients showed a risk that was about two-fold that of the one to be expected in the general population. By contrast, a decrease in the total risk was observed in patients treated with tamoxifen. Patients who received chemotherapy and tamoxifen as well as those in the no-treatment group showed a risk which was comparable to that of the general population.
Conclusions: Adjuvant chemotherapy appears to increase the risk of second malignancies. By contrast, tamoxifen seems to exert an overall protective effect in this regard, and it also appears to counteract, at least partially, the carcinogenic effect of chemotherapy.
Implications: While there is plenty of evidence that the benefit achieved by adjuvant chemotherapy considerably exceeds the risk of second malignancies, the indiscriminate use of chemotherapy should be avoided, particularly in patients with a low risk of relapse. Moreover, it seems reasonable to prefer tamoxifen over chemotherapy for patients likely to obtain comparable therapeutic benefit from antiestrogenic treatment.

Adjustment among husbands of women with breast cancer
Carol Noll Hoskins, Ph.D., RN, F.A.A.N., Sonia Baker, Ph.D., R.N., Wendy Budin, Ph.D., R.N., David Ekstrom, Ph.D., R.N., Greg Maislin, M.S., MA, Deborah Sherman, Ph.D., R.N., Jean Steelman-Bohlander, Ph.D., R.N., Marilyn Bookbinder, Ph.D., R.N., Cynthia Knauer, M.S., R.N.

The effect of marital support and support from other adults on the emotional and physical adjustment of 121 husbands of women with breast cancer was examined. Role function and satisfaction with health care also were evaluated as predictors of adjustment.
Intact data series were obtained at 7-10 days and at 1, 2, 3, 6, and 12 months after surgery. Emotional adjustment could be predicted by satisfaction with the patient’s response to interactional and emotional needs and by support from other adults. The relationships were significant at concurrent times, across contiguous times, and predictive from the 7-10 day postsurgical period to both the 6-month and one-year end points. Although physical adjustment was predicted by support only at selected times, satisfaction with health care was predictive of perceived overal health status at five of the six data-collection periods. Functional status in vocational, domestic, and social roles was significantly related to emotional adjustment at all times with few exceptions and to physical adjustment at selected times. Type of surgery and stage of disease had an effect on selected physical and emotional outcomes over time.

Base-line quality-of-life assessment in the national surgical adjuvant breast and bowel project breast cancer prevention trial
Patricia A. Ganz, Richard Day, John E. Ware, Jr., Carol Redmond, Bernard Fisher*

Background: The Breast Cancer Prevention Trial (BCPT) is a large, multicenter chemoprevention trial testing the efficacy of the antiestrogen drug tamoxifen for prevention of breast cancer and coronary heart disease in healthy women at high risk of breast cancer. The BCPT evolved from a series of prior studies in early stage breast cancer demonstrating the efficacy of tamoxifen in the prevention of systemic breast cancer recurrence and in the reduction of contralateral breast cancers. Purpose: The purpose of this article is to describe the methodologic considerations in the collection of health-related quality-of-life (HRQL) data in the BCPT and to present base-line HRQL data on the first 9749 participants. Methods: An HRQL questionnaire that included the Center for Epidemiologic Studies-Depression Scale, a symptom checklist, the Medical Outcomes Study 36-item short form (MOS-SF-36), and the MOS sexual problems questions was completed by participants in the BCPT at base line (prior to random assignment). Medical and demographic information, as well as projected risk of breast cancer, were collected as part of study eligibility. Descriptive and correlational data were examined for these study participants. Results: BCPT participants report high levels of functioning compared with U.S. general population norms but still report an average of 8.9 distinct symptoms during the past 4 weeks. Depression is less prevalent among the participants than in community samples, which reflects the exclusion of clinically depressed individuals. Sixty-five percent reported being sexually active in the past 6 months, with an age-related decline in sexual activity. Younger women reported fewer sexual problems than older women. There is a strong correlation between the two mental health measures, moderate to weak correlations between HRQL scales and levels of self-reported symptoms, and only weak correlations between measures of breast cancer risk and HRQL scales. The MOS-SF-36 scores were examined for three consecutive recruitment samples (0-6 months, 7-12 months, and 13-20 months), and the base-line scores were slightly better for the earliest group of participants. Conclusions: This article demonstrates the feasibility of collecting HRQL data in a large, multicenter, chemoprevention trial for women at high risk of breast cancer. The successful integration of HRQL data collection into this clinical trial attests to its value as a safety-monitoring end point and as an explicit and measurable outcome for the entire trial. Implications: HRQL data are important for studies in which healthy populations are involved and in which the potential for decrements in quality of life are real or perceived.

Background: To date, anthracyclines are the most active drugs against breast tumors, and the taxane paclitaxel (Taxol) looks very promising. Both classes of drugs are affected by cellular multidrug-resistance mechanisms, and therefore their sequential use raises the possibility of clinical cross-resistance. It is therefore important to assess the activity of paclitaxel in patients with clinical resistance to anthracyclines. Purpose: We assessed the safety and efficacy of paclitaxel administered by the logistically convenient 3-hour infusion to breast cancer patients who had disease progression within 12 months since prior therapy with anthracyclines. Methods: Fifty-one patients with metastatic breast cancer who had all relapsed or whose disease had progressed within 12 months from completion of an anthracycline-containing chemotherapy protocol (six receiving adjuvant therapy, 19 receiving neoadjuvant therapy, and 26 receiving treatment for metastatic disease) were enrolled in this phase II trial from June 1992 to May 1994. After medication to prevent type I acute hypersensitivity reactions, paclitaxel was given intravenously over 3 hours at 175 mg/m2 to the first 15 patients and at 225 mg/m2 to the next 36 patients. The median age was 50 years (range, 31-62 years), and the median Eastern Cooperative Oncology Group performance status was 0 (range, 0-2). Results: Patients received a median of five cycles (range, one to 11 cycles). After initial doses of 175 and 225 mg/m2, paclitaxel could be increased by 25 mg/m2 in 73% and 58% of cycles, respectively. Among 50 assessable patients, seven achieved a complete response and 12 achieved a partial response (response rate, 38% [95% confidence interval = 25% - 53%]). The median duration of response was 7 months (range, 4-16 months), and the median time to disease progression for all patients was 5 months. Grade 4 neutropenia occurred in 3% of the cycles and in 12% of the patients and was never associated with fever and infection. Common toxic effects were myalgia and arthralgia (94% of the patients; 4% grade 3), peripheral neuropathy (92% of the patients; 8% grade 3), and alopecia (all patients). Pruritus and neuropathy were significantly more frequent and severe, respectively, with the higher dose (P < .01 by c2 test). Frequency and severity of other toxic effects were similar at either starting dose. Ten patients had symptoms of neuro-optic toxicity. Only one patient had a grade 2 hypersensitivity reaction. Conclusions: Paclitaxel at starting doses of 175 and 225 mg/m2 given as a 3-hour infusion can safely be administered to, and is active in women whose disease has progressed after prior treatment with anthracyclines. There was evidence of increased toxicity at the higher dose but no suggestion of better efficacy. Implication: Paclitaxel by a 3-hour infusion in combination with doxorubicin should be investigated in patients with metastatic breast cancer. Unless randomized trials demonstrate greater efficacy of the more toxic higher dose, it is suggested that a dose of 175-200 mg/m2 be administered with the 3-hour infusion schedule.

Long-term follow-up of elderly patients with operable breast cancer treated with surgery without axillary dissection plus adjuvant tamoxifen
G. Martelli, G. DePalo¹, N. Rossi², D. Coradini³, P. Boracchi², E. Galante1 and G. Vetrella¹
Divisions of ¹Diagnostic Oncology and Outpatient Clinic, ²Statistics and ³Experimental Oncology C. Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy

Between 1982 and 1990, 321 elderly patients (range 70-92 years, median age 77) with operable breast cancer (T1 in 219, T2 in 77, T3 in one and T4b in 24 patients) and clinically uninvolved axillary nodes underwent surgery without axillary dissection and received adjuvant tamoxifen. All patients had surgery performed under local anaesthesia. Tamoxifen was given after surgery at the dose of 20 mg daily, indefinitely. With a median follow-up of 67 months (range 42 - 141), 17 patients developed local relapse, 14 ipsilateral axillary recurrence, five ipsilateral breast cancer, five contralateral breast cancer, 13 second primary and 23 developed distant metastases. The cumulative probability of developing a local, axillary and distant recurrence at 72 months was estimated to be 5.4%, 4.3% and 6.2%, respectively. Out of 244 patients who did not develop any relapse, 83 (25.8%) died from intercurrent disease. The 72 month relapse-free survival rate was 76%. This experience suggest that elderly patients with small tumours without clinical axillary involvement may be satisfactorily treated with conservative surgery and tamoxifen. The importance of axillary dissection is controversial owing to a high response rate to hormonal therapy and an increased death rate due to concomitant diseases.

Melanoma
Jason K. Rivers

Melanoma is now the most rapidly increasing cancer in white populations1. For example, in Canada over the past 25 years the incidence of melanoma has doubled among women and more than doubled in men2. Mortality rates have been falling in some populations, especially in younger people, possibly due to earlier detection of disease1. Melanoma has become a major public-health concern.
Epidemiology
Less than 20 years have passed since the first case-control studies linking sun exposure to melanoma induction were published. In 1992, the International Agency for Research on Cancer, in a comprehensive review, concluded “there is sufficient evidence in humans for the carcinogenicity of solar radiation. Solar radiation causes cutaneous melanoma”3. Armstrong and Cricker have estimated that 80% or more of melanomas are caused by sun exposure, even in white populations living in areas of low solar irradiance and with a low incidence of melanoma. Although the mechanism remains unclear, it does seem that acute, intense exposure to sunlight, especially exposure that causes erythema and inflammation (sunburn), is strongly linked to the development of melanoma5. Individuals who have had melanoma are twice as likely to have experienced at least one episode of severe sunburn and are more than three times as likely to report several episodes of severe sunburn, as those with no history of the disease. However, epidemiological evidence that sunburn early in life carries a higher risk of melanoma remains limited5, 6. 20% of the world’s melanomas are in black Africans and Asians and are not clearly associated with sunlight4. The pathogenesis of melanoma in these populations deserves scruntiny.
Studies of occupational and environmental factors related to melanoma have been inconclusive. An association with higher incomes may simply reflect greater opportunity to holiday abroad in the sun7. There is no strong evidence of a relation between diet, alcohol, or vitamin A, ß-carotene, and related compounds in the pathogenesis of melanoma8.

The role of biological therapy (Chapter 3)

A wide variety of biological agents have the capacity to enhance or supplement host antitumor immune activity, and there is convincing evidence that melanoma may be suitable for immunological manipulation (see section on biological therapy in Chapter 2). The clinical application of biological agents is a major advance in the treatment of melanoma, bringing an important addition to the therapeutic armamentarium for this disease. The first part of this chapter considers biological agents that have been used as single agents in the treatment of melanoma; next follows a discussion on the role of biological agents in combination therapy. Particular emphasis is given to interferon a (IFNa-) - the most extensively studied biological agent in clinical use1, 2 - which has proven efficacious as a systemic monotherapy in metastatic disease, as an adjuvant to surgery in patients at high risk of relapse, and a component of combination regimens for metastatic disease.
Biological agents that have been investigated for use as monotherapy in melanoma include cytokines (such as interferon, interleukins, and TNF), nonspecific immunostimulants, tumor vaccines, monoclonal antibodies, and adoptive immunotherapy. Clinical experience with single-agente biological therapies in melanoma is summarized in Table 1.

Long-term survival results for patients with locally advanced, initially unresectable non-small cell lung cancer treated with aggressive concurrent chemoradiation
Corey J. Langer, M.D., Walter J. Curran, M.D., Steven M. Keller, M.D., Robert B. Catalano, M.D., Samuel Litwin, M.D., Kenneth B. Blankstein, M.D., Naomi Haas, M.D., Sheri N. Campli, R.N., Robert L. Comis, M.D., Philadelphia, Pennsylvania

Purpose
Patients with locally advanced, initially unresectable non-small cell lung cancer (NSCLC) have a median survival time of 9 to 11 months, a 2-year survival rate of 13%, and a long-term survival rate of 5% to 7% when treated with radical thoracic radiation alone. Because of the preclinical radiosensitizing capabilities of 5-fluorouracil and cisplatin and the therapeutic synergy of etoposide and cisplatin, we combined these agents with full-dose radical thoracic radiation to determine the feasibility and efficacy of this approach in locally advanced NSCLC.
Metods
Patients with clinical stage IIIb and bulky IIIa NSCLC and ECOG performance status 0 or 1 received 5-fluorouracil infusion (640-800 mg//m2/d CVI days 1-5, 29-34), cisplatin (20 mg/m2/d, days 1-5, 29-34), etoposide (50 mg//m2, days 1, 3, 5, 29, 31, 33) and concurrent thoracic radiation (60 Gy/2 Gy/d/30 Fx). Patients with adequate cytoreduction proceeded to surgical resection.
Results
From March 1987 to July 1990, 41 patients were enrolled on study; 40 are evaluable. The objective response rate was 90%. Thirteen patients (39%), five with clinical stage IIIb disease and eight with IIIa disease, underwent thoracotomy and resection; three proved to have pathological complete remissions. Ten of 77 chemotherapy courses were complicated by neutropenic fever. Grade 3 or 4 esophagitis occurred in 21 patients (52%). Cardiac ischemia or infarction occurred in two patients (5%). There were seven deaths in the first 6 months in the absence of disease progression. Two-year survival was 38%, 3-year survival 25%, and 4- to 5-year survival 18%. Six patients (15%) remain alive at the median follow-up time of 66 months (range, 64-84).
Conclusions
Despite substantial early morbidity and mortality, concurrent, aggressive chemoradiation produced a long-term survival rate in locally advanced NSCLC comparable to other combined modality approaches. However toxicity, particularly esophagitis and postoperative complications, preclude the use of this regimen in phase III studies. Combined modality approaches for locally advanced, initially unresectable NSCLC have become standard; research must simultaneously focus on ways to enhance efficacy and reduce toxicity.

Non-small cell lung cancer: An overview of diagnosis, stagint, and treatment
Kerry V. Harwood

Objectives: To review the current status, recent advances and ongoing research efforts related to screening, diagnosis and staging, and treatment of non-small cell lung cancer (NSCLC).
Data sources: Research studies, review articles, and abstracts relating to NSCLC.
Conclusions: Surgery is curative in a small number of patients. Radiation therapy can often control local disease and palliate symptoms; however, it does not impact overall survival. Current chemotherapy regimens have demonstrated ability to prolong survival when compared to “best supportive care” ; however, survival benefit is limited to a period of a few weeks or months.
Implications for nursing practice: An understanding of treatment modalities and new therapies for NSCLC will help nurses assist patients to make educated decisions about the potential risks and benefits of their therapeutic options.

13/19 - Acta Oncologica, 35: 733-736, 1996

Paclitaxel (Taxol) monotherapy in the treatment of progressive and recurrent ovarian carcinoma after platinum-based chemotherapy
René Blom, Niklas Palm and Ernst Simonsen

This retrospective study evaluates paclitaxel (Taxol) monotherapy in the treatment of advanced ovarian cancer, previously treated with cisplatin. Forty-six patients with FIGO stage IC to IV were given Taxol in doses of 175 mg/m2 and 135 mg/m2 as a 3-h continuous infusion. All patients were given premedication (prednisone, clemastin, cimetidine) to prevent hypersensitivity reactions. One allergic reaction was observed. Thirty-nine patients showed progress of their disease during treatment and seven showed a response (overall response rate 15.2%; 95% c.i. 4.8-25.6%). There were five total (10.9%) and two partial responses. Among 20 patients who had progressed during or within 6 months of prior cisplatin-based therapy two were responders and two showed partial response (10%). Among 26 patients who had responded to cisplatin but suffered recurrence more than 6 months after cisplatin treatment, there were five total responders (19.2%). We conclude that Taxol treatment does not alter the fact that advanced ovarian carcinoma still carries a grave prognosis. Taxol monotherapy treatment of patients not responding to first line platinum treatment or having relapse within six months of completed therapy, seems to have a limited effect. For those patients responding to the first line platinum treatment that lasts for at least six months the effect of Taxol treatment is more encouraging.

Chemotherapy and radiotherapy in locally advanced cervical cancer
Joan Bruntet, Carmen Alonso, Marta Llanos, Adelaida Lacasta, Josefina Fuentes, Luis A. Mendoza, Josep M. Badia, Enrique Delgado and Belen Ojeda

Radiotherapy has been standard therapy for locally advanced squamous cell cervical cancer. Neoadjuvant chemotherapy is being studied to improve responses and survival. We report a phase II study in locally advanced squamous cell cervical cancer (FIGO stages III and IVA) using chemotherapy with bleomycin, methotrexate and cisplatin (BMP) followed by radical radiotherapy. Of the 35 patients, 31 in stage III and 4 in stage IVA, 3 complete responses (CR) and 22 partial responses (PR) were achieved after chemotherapy treatment. Thirty-one patients completed radiotherapy; 19 achieved CR and 4 PR. Five-year actuarial survival for the entire group was 45% (95% confidence interval, 37-53%) with a median survival of 56 months. Patients with CR had a significantly better survival: the 5-year actuarial survival was 74% (95% CI, 59-89%). Recurrence developed in 4 of 19 patients. The most frequent side-effects were nausea and vomiting. Myelosuppression and impaired renal function also occurred. There was no evidence of radiotherapy toxicity enhancement. The stage and Karnofsky index were significant prognostic factors. It is concluded that BMP chemotherapy in advanced cervical cancer is effective and, followed by radiotherapy, allows a good control of this tumor. The group of patients with complete response have a low rate of recurrences and a long survival chance.

Endometrial carcinoma
Peter G. Rose, M.D.

Uterine cancer is the fourth most frequent cancer in women, with an estimated 34,000 cases and 6000 deaths in the United States in 19961. It is the most curable of the 10 most common cancers in women and the most frequent and curable of the gynecologic cancers. Ninety-seven percent of all cancers of the uterus arise from the glands of the endometrium and are known as endometrial carcinomas. The remaining 3 percent of uterine cancers are sarcomas, which are not discussed here. Numerous changes in the pathological description of endometrial cancer, identification of prognostic variables, staging, and treatment have occurred in the past 15 years. This article will review the current understanding of the epidemiology, diagnosis, prognostic factors, and initial treatment of endometrial carcinoma.

The importance of a multidisciplinary group in the treatment of soft tissue sarcomas
T. Wiklund¹, R. Huuhtanen¹, C. Blomqvist¹, E. Tukiainen², M. Virolainen¹, P. Virkkunen¹, S. Asko-Seljavaara², J.M. Björkenheim³ and I. Elomaa^1
1Department of Radiotherapy and Oncology; ²Department of Plastic Surgery; and ³Department of Orthopaedics and Traumatology, Helsinki University Hospital, FIN-00290 Helsinki, Finland

In 1987, a multidisciplinary soft tissue sarcoma (STS) group was established and a treatment protocol was set up. By 1993, there were 193 patients with a diagnosis of STS of the superficial trunk or extremities. 134 patients were referred with primary (stage M0) tumours and treated with curative or palliative intention. Nine amputations were performed. 94 (70%) patients were treated with wide or compartment surgery (n = 62) or marginal surgery combined with postoperative radiotherapy (n = 32). According to the protocol, these patients had received adequate treatment. 18 patients have recurred locally (13%) (median follow-up: 36 months). 12 were salvaged. 33 had metastases. The estimated 3-year survival, local control and disease-free survival rates are 79, 87 and 69%, respectively. These results compare favourably with previously published results from this hospital and from a nationwide study. The improved results emphasise the importance of a multidisciplinary STS group.

Pelvic autonomic nerve preservation for patients with rectal carcinoma Oncologic and functional outcome
Kenichi Sugihara, M.D., D.M.Sc., Yoshihiro Moriya, M.D., D.M.Sc., Takayuki Akasu, M.D., Shin Fujita, M.D., D.M.Sc.
Colorectal Division, Departament of Surgery, National Cancer Center Hospital, Tokyo, Japan

Background. Serious problems in the surgical treatment of patients with rectal carcinoma are local failure and urinary and sexual dysfunction. To resolve these problems, pelvic autonomic nerve preservation (PANP) combined with lateral lymph node dissection has been introduced.
Methods. Of 238 consecutive patients with middle or low rectal carcinoma who underwent potentially curative surgery between 1987 and 1992, 214 underwent PANP according to pre- and intraoperative staging. PANP was evaluated from the perspectives of oncologic outcome and urinary and male sexual function with a retrospective questionnaire in a group of patients followed prospectively.
Results. During the median follow-up of 53 months, local recurrence developed in 5.6% of patients; no local recurrence was observed in Dukes Stage A or Dukes Stage B patients. The 5-year survival rates of Dukes Stage A (n = 55), Dukes Stage B (n = 72), and Dukes Stage C (n = 87) patients were 96.4%, 84%, and 67.3%, respectively. Of patients undergoing preservation of the unilateral; pelvic plexus alone, 93.5% maintained the ability to void spontaneously. Of patients who had complete preservation of the autonomic nerve system, 70.4% maintained male sexual function, and of patients who had removal of the hypogastric nerves and preservation of the pelvic nerve plexuses, 66,7% were capable of erection and intercourse without normal ejaculation.
Conclusions. Early stage rectal carcinoma should be treated both with local cure and complete preservation of urinary and sexual function. In high risk patients with suspected perirectal lymph node metastases and tumors invading the perirectal fat, the appropriate PANP should be applied with consideration of the balance between achieving a cure and preserving autonomic function. [See Editorial on pages 1847-50, this issue.]

Evaluation of multimodality treatment of locoregional esophageal carcinoma by southwest oncology group 9060
Elizabeth A. Poplin, M.D.¹, Joth Jacobson, M.S.², Arnold Herskovic, M.D.³, Timothy J. Panella, M.D.⁴, Manuel Valdivieso, M.D.⁵, Laura F. Hutchins, M.D.⁶, John S. Macdonald, M.D.⁷

Background. Continuous infusion 5-fluorouracil (CI5-FU) has been utilized concurrently with radiotherapy to improve tumor control. In this pilot trial, cisplatin, CI5FU, and radiotherapy were utilized for the treatment of locoregional esophageal carcinoma. It was postulated that the combination would be well tolerated and associated with high response rate and survival duration.
Methods. Thirty-two eligible patients with locoregional squamous cell carcinoma and adenocarcinoma of the esophagus received a regimen consisting of the following: radiotherapy, 50 Gray (Gy) (30 Gy anteroposterior/posteroanterior regional with 20 Gy AP/LPO/RPO boost) over 5 weeks, with CI5-FU 250 mg/m2/d for the duration of radiotherapy and cisplatin 25 mg/m2/day on Days 1-3 during Weeks 1 and 4 of the radiotherapy cycle. Upon completion of radiotherapy, two additional courses of cisplatin 75 mg/m2 on Days 1 and 29 and CI5-FU 300 mg/m2/day on Days 1-21 and 29-50 were delivered. Following imaging and endoscopic reassessment, patients with no evidence of disease received more chemotherapy. Surgery was suggested only for patients with residual local disease.
Results. Complete response was demonstrated in 44% of patients, clinically in 12 patients, and during surgery in 2 others. The median survival was 20 months, and the 1-year survival rate was 59%. Toxicity was severe, comprised of esophagitis, infection, and gastrointestinal complications. Dose delays and reductions occurred in the majority of patients. Four early deaths were noted.
Conclusions. The regimen that was the focus of this trial has been active in the treatment of esophageal carcinoma. However, compared with existing regimens, its complexity and toxicity preclude its future use without modifications.

Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer
Meta-Analysis Group in Cancer*

Background: Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear. Purpose: A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival. Methods: The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of a stratified logrank test. Multivariate analyses were performed with the use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators. Results: The tumor response rate was 41% for patients allocated to HAI with FUDR (complete response [CR], 3%; partial response [PR], 38%) compared with 14% for patients allocated to IVC with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16-0.40; P < 1010). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when all trials were taken into account (P = .-0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14). Conclusion: These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer. Implications: The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.

Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial
A. Cuschieri, P. Fayers, J. Fielding, J. Craven, J. Bancewicz, V. Joypaul, P. Cook, for the Surgical Cooperative Group*

Background. In Japan the surgical approach to treatment of potentially curable gastric cancer, including extended lymphadenectomy, seems in retrospective surveys to give better results than the less radical procedures favoured in Western countries. There has, however, been no evidence from randomised trials that extended lymphadenectomy (D2 gastric resection) confers a survival advantage. This question was addressed in a trial involving thirty-two surgeons in Europe.
Methods. In a prospective randomised controlled trial, D1 resection (level 1 lymphadenectomy) was compared with D2 resection (levels 1 and 2 lymphadenectomy). Central randomisation (200 patients in each arm) followed a staging laparotomy.
Findings. The D2 group had greater postoperative hospital mortality (13% vs 6.5%; p = 0.04) [95% Cl 9-18% for D2, 4-11% for D1] and higher overall postoperative morbidity (46% vs 28%; p < 0.001); their postoperative stay was also longer. The excess postoperative morbidity and mortality in the D2 group was accounted for by distal pancreaticosplenectomy and splenectomy. In the whole group (400 patients), survival beyond three years was 30% in patients whose gastrectomy included en-bloc pancreatico-splenic resection versus 50% in the remainder.
Interpretation. D2 gastric resections are followed by higher morbidity and mortality than D1 resections. These disadvantages are consequent upon additional pancreatectomies and distal splenectomies, and in long-term follow-up the higher mortality when the pancreas and spleen are resected may prove to nullify any survival benefit from D2 procedures.

Prognostic variables in patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy
George Fountzilas, M.D., Konstantinos Gossios, M.D., Alkis Zisiadis, M.D., Eugenia Svarna, M.D., Dimosthenis Skarlos, M.D., and Nicholas Pavlidis, M.D.

Possible prognostic variables for tumor response, time to progression (TTP), and survival in 141 patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy were analyzed. None of the variables examined for their possible influence on tumor response attained significance in the stepwise logistc regression. In the univariate analysis, variables found to be strongly associated with TTP were performance status ( PS) (P = 0.0031), liver involvement (P = 0.030), and the initial values of WBC (P = 0,039), lactic dehydrogenase (LDH; P = 0.0053), g-glutamyl-transpeptidase (g-GT; P-0.0013), alkaline phosphatase (ALP; P = 0.0186), albumin (P = 0.0004), and carcinoembryonic antigen (CEA; P = 0.0014). In the Cox analysis, liver involvement (P = 0,0553), albumin (P = 0.0181), PS (P = 0.0484), and ALP (P = 0.0553) were retained as independently significant variables. When only patients with liver metastases were included in the analysis, then only albumin (P < 0.001) demonstrated a prognostic significance. Also, in the univariate analysis, variables predicting survival were PS (P = 0.0230), grade (P = 0.0060), liver involvement (P = 0.0002), LDH (P = 0.0001), g-GT (P < 0.001), ALP (P = 0.0006), albumin (P = 0.0309), and CEA (P = 0.0005). With the multivariate analysis, g-GT (P = 0.0004), albumin (P = 0.0634); and CEA (P = 0.0804) were selected as significant. In those patients who presented with liver involvement, variables predicted survival were g-GT (P = 0.0041), albumin (P = 0.0442), and the percentage of involved liver parenchyma (P = 0.0690). These results could be helpful for the stratification of future trials in advanced colorectal cancer. © 1996 Wiley-Liss, Inc.

Surveillance versus adjuvant chemotherapy in stage I non-seminomatous testicular cancer: a decision analysis
A.M. Stiggelbout¹, G.M. Kiebert¹, J.C.J.M. de Haes¹, ³, H.J. Keizer², G. Stoter ⁴, R. de Wit⁴, J.B. Vermorken⁵, J.W. H. Leer² and J. Kievit<sup>1

1</sup>Medical Decision Making Unit, Leiden University Hospital K-6-R; ²Department of Clinical Oncology, Leiden University Hospital K-1-P, P.O. Box 9600, 2300 RC, Leiden; ³Department of Medical Psychology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam; ⁴Department of Medical Oncology, Rotterdam Cancer Institute/Daniël den Hoed Kliniek, P.O. Box 5201, 3008 AE, Rotterdam; and ⁵Department of Internal Medicine, Hospital of the Free University, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands

In stage I non-seminomatous testicular cancer, the decision between surveillance and adjuvant chemotherapy rests heavily upon the valuation of quality of life. Decision analysis was used to assess at what relapse rate adjuvant chemotherapy is preferred when patients’ and clinicians’ valuations are considered. Probabilities were obtained from the literature and from experts. Valuations of the disease states were obtained from patients (n = 68) and clinicians (n = 50). Results from the model were compared with a treatment preference question, asking for the relapse rate directly. Adjuvant chemotherapy was preferred at relapse rates above 50% when patient valuations were used. The valuations of the disease states had a strong impact on the decision. Using clinician valuations adjuvant chemotherapy was preferred at relapse rates above 73%. The relapse rates from the treament preference question were lower; 46% for patients and 35% for clinicians. The results indicate that when patient preferences are accounted for, adjuvant chemotherapy should be considered more often. Copyright © 1996 Elsevier Science Ltd.
Key words: testicular cancer; quality of life; patient preferences; medical decision making; adjuvant chemotherapy; surveillance

Local control after radiation for prostatic carcinoma: significance and assessment
Deborah A. Kuban and Anas M. El-Mahdi

Local tumor control is of great importance in the definitive treatment of prostatic carcinoma. Not only is if the best measure of radiation efficacy but its significance in terms of the related morbidity and mortality of tumor recurrence has been clearly shown. On this we would all likely agree. More controversial, however, is the definition of local failure and the manner in which this determination is made. Having until recently largely referred to clinical findings by rectal exam, prostate-specific antigen (PSA), ultrasound, and biopsy findings have, of late, presented additional information. Whether data from these evaluations should expand our current definition of local failure is as yet undecided. Surely their predictive value is less disputable. Of prime consideration is the practicality of therapeutic options for disease recurrence. By virtue of their age and initial tumor stage, the majority of patients with local failure after irradiation, including chemical (PSA) and microscopic (positive biopsy) failure, are unlikely to be good surgical candidates. Thus, salvage surgery, like repeat irradiation has questionable benefit and a relatively high risk of significant complications. Although hormonal therapy is fairly innocuous, there is no evidence as yet that treating subclinical disease is advantageous. Therefore, with this particular malignancy that affects men who often die of competing causes with incidental microscopic cancer totally undiagnosed, a pragmatist might prefer to think in terms of clinical cure. However, thjat is not to say that we will give up our continuing efforts toward improving radiation efficacy and enhancing the therapeutic ratio.

A prospective study of smoking and risk of prostate cancer
Hans-Olov Adami¹, ³, ⁷, Reinhold Bergström¹, ², Göran Engholm⁴, Olof Nyrén¹, Alicja Wolk, Anders Ekbom¹, ³, Anders Englund⁵ and John Baron¹, ⁶
Departments of ¹Cancer Epidemiology and ²Statistics, Uppsala University, Uppsala, Sweden; ³Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; ⁴National Board of Health and Welfare, Stockholm; ⁵National Board of Occupational Safety and Health, Stockholm, Sweden; ⁶Department of Medicine and Community and Family Medicine, Dartmouth Medical School, Hanover, NH, USA.

We evaluated the hypothesis that smoking increases the incidence of and mortality from prostate cancer. High-quality smoking information was collected in 1971-1975 in a nation-wide cohort of 135,006 male construction workers in Sweden. We achieved virtually complete follow-up through record link-ages and ascertained as of December 1991 2,368 incident cases of prostate cancer and 709 deaths due to this disease. Rate ratios (RR) of prostate cancer incidence and mortality, with 95% confidence intervals (CI), were estimated in Poisson-based age-adjusted models, with amount and duration of smoking as independent variables. We found no convincing association between current smoking status, number of cigarettes smoked or years since onset and risk of prostatic cancer. The age-adjusted incidence RR among previous smokers was 1.09 and among current smokers 1.11 compared with non-smokers. Weak and inconsistent trends were seen with increasing number of cigarettes smoked per day and increasing duration among current smokers. Smokers of 15 or more cigarettes daily for at least 30 years experienced an incidence RR of 1.30. Mortality in ex-smokers was similar to that in never-smokers; it was, however, slightly increased among current smokers with-out any trend with amount smoked or duration. The weak and inconsistent associations between smoking and prostate cancer could easily have arisen due to bias or confounding. We therefore conclude that smoking is most likely not causally linked to the occurrence of prostate cancer.