 Volume 47 n° 2 |
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Predictors of Quality of Life in Rural Patients With Cancer
Quality of life (QOL) as an outcome for cancer treatment has been studied primarily in urban populations. Yet, descriptions of rural dwellers suggest that their perception of QOL may differ from that of their urban counterparts. The purpose of this study was to examine QOL in people with a cancer diagnosis of at least 1 month duration in two similar rural northeastern states. The Functional Assessment of Cancer Therapy General (FACT G) scale was completed by 344 respondents. The mean QOL score was 89.41 ± 16.55. State of residence, gender, known recurrence, and marital status were significant predictors of QOL, explaining 18.3% of the variance in this study. Age, education level, income, type of cancer, living arrangements, and time since diagnosis were not predictive. The QOL scores in this rural sample were higher than those reported earlier for predominantly urban dwellers. Future research is needed to understand these differences.
Keywords: Cancer Quality of life Rural
Quality of Life for Long-Term Survivors of Cancer
Influencing Variables: The study’s purpose was to describe the relations among self-esteem, learned resourcefulness, and social support, and to show how they predict health-related quality of life (HRQL) for long-term survivors of cancer. With advances in oncology and increased survival, variables influencing the HRQL of long-term survivors of cancer must be explored. The design was descriptive and correlational. Five instruments were sent to 456 long-term survivors in southern California. Data were analyzed for 62 of 111 consenting individuals, most of whom were married, retired, white, college-educated, female survivors of breast cancer older than 60 years of age treated by radiation and surgery. Subjects with higher self-esteem reported higher HRQL (r = 0.69; p = 0.00). Learned resourcefulness had a significant negative relation with HRQL (r = -0.32; p = 0.01). Social support was operationalized as functional components, network properties, and recent loss. Only the loss component of social support had a significant negative relation with HRQL (r = -0.38; p = 0.00). Together, the three variables explained more than half of the variance (R2 = 0.53) of HRQL, with self-esteem being the strongest predictor. The HRQL of long-term survivors of cancer may increase with interventions such as both survivor- and nurse-led support groups aimed at supporting and improving self-esteem. In addition, education to anticipate social support losses may further enhance HRQL.
Keywords: Health-related quality of life Learned resourcefulness Long-term cancer survivor Self-esteem Social support.
Assessment of depression among cancer patients: the role of pain, cancer type and treatment
One hundred consecutive cancer patients were assessed using two structured methods for assessing major depressive disorder-Structured Clinical Interview for DSM III-R (SCID) and Endicott criteria-and using a depression rating scale-Hamilton Depression Rating Scale (HAMD).
Forty-nine percent of patients were depressed using SCID (DSM III-R criteria), whereas 29% of patients were depressed using Endicott criteria. Twenty-eight percent of patients were depressed using both criteria. Age and sex did not have any influence on the assessment of major depression. Both the structured interview and the rating scale were able to identify suicide ideation. Depressed patients were not shown to have more lifetime depression than non-depressed patients using both structured methods. Patients who were depressed using both assessments of depression had more metastasis and pain than non-depressed patients.
Dexamethasone alone or in combination with Ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy
Background: The prevention of delayed nausea and vomiting caused by moderately emetogenic chemotherapy for cancer has not been studied systematically.
Methods: We enrolled patients who were scheduled to receive chemotherapy for the first time in a double-blind, randomized, multicenter study. All the patients received ondansetron combined with dexamethasone for prophylaxis against emesis that might occur within 24 hours after the start of chemotherapy (acute emesis). They were then divided into two groups: patients who did not have either vomiting or moderate-to-severe nausea (the low-risk group) and patients who had one or both (the high-risk group). Patients in the low-risk group were then randomly assigned to one of the following regimens, given on days 2 through 5 after the start of chemotherapy: oral placebo, 4 mg of dexamethasone given orally twice daily, or 8 mg of ondansetron in combination with 4 mg of dexamethasone, given orally twice daily. Patients in the high-risk group were randomly assigned to receive oral dexamethasone alone or in combination with ondansetron at the same doses as those used in the low-risk group.
Results: Among the 618 patients in the low-risk group, there was a complete absence of both delayed vomiting and moderate-to-severe nausea in 91.8 percent of those who received ondansetron combined with dexamethasone, 87.4 percent of those who received dexamethasone alone, and 76.8 percent of those who received placebo. The proportions of patients who were protected by dexamethasone combined with ondansetron or by dexamethasone alone were significantly greater than the proportion protected by placebo (P<0.001 and P<0.02, respectively). Of the 87 patients in the high-risk group, complete protection was achieved in 40.9 percent of those treated with ondansetron and dexamethasone and in 23.3 percent treated with dexamethasone alone (P not significant).
Conclusions: The best way to prevent delayed nausea and vomiting in patients receiving moderately emetogenic chemotherapy is to control these complications within the first 24 hours after the start of chemotherapy. Dexamethasone alone provides adequate protection against delayed emesis in patients at .low risk (those who have not had acute emesis).
The effect of Celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis
Background: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2.
Methods: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line.
Results: At base line, the mean (±SD) number of polyps in focal areas where polyps were counted was 15.5±13.4 in the 15 patients assigned to placebo, 11.5±8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3±8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups.
Conclusions: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor; leads to a significant reduction in the number of colorectal polyps.
Irinotecan plus Fluorouracil and Leucovorin for metastatic colorectal cancer
Background: The combination of fluorouracil and leucovorin has until recently been standard therapy for metastatic colorectal cancer. Irinotecan prolongs survival in patients with colorectal cancer that is refractory to treatment with fluorouracil and leucovorin. In a multicenter trial, we compared a combination of irinotecan, fluorouracil, and leucovorin with bolus doses of fluorouracil and leucovorin as first-line therapy for metastatic colorectal cancer. A third group of patients received irinotecan alone.
Methods: Patients were randomly assigned to receive irinotecan (125 mg per square meter of body- surface area intravenously), fluorouracil (500 mg per square meter as an intravenous bolus), and leucovorin (20 mg per square meter as an intravenous bolus) weekly for four weeks every six weeks; fluorouracil (425 mg per square meter as an intravenous bolus) and leucovorin (20 mg per square meter as an intravenous bolus) daily for five consecutive days every four weeks; or irinotecan alone (125 mg per square meter intravenously) weekly for four weeks every six weeks. End points included progression-free survival and overall survival.
Results: Of 683 patients, 231 were assigned to receive irinotecan, fluorouracil, and leucovorin; 226 to receive fluorouracil and leucovorin; and 226 to receive irinotecan alone. In an intention-to-treat analysis, as compared with treatment with fluorouracil and leucovorin, treatment with irinotecan, fluorouracil, and leucovorin resulted in significantly longer progressionfree survival (median, 7.0 vs. 4.3 months; P=0.004), a higher rate of confirmed response (39 percent vs. 21 percent, P<0.001), and longer overall survival (median, 14.8 vs. 12.6 months; P=0.04). Results for irinotecan alone were similar to those for fluorouracil and leuco- vorin. Grade 3 (severe) diarrhea was more common during treatment with irinotecan, fluorouracil, and leu-covorin than during treatment with fluorouracil and leucovorin, but the incidence of grade 4 (life-threat ening) diarrhea was similar in the two groups (<8 per cent). Grade 3 or 4 mucositis, grade 4 neutropenia, and neutropenic fever were less frequent during treat ment with irinotecan, fluorouracil, and leucovorin. Adding irinotecan to the regimen of fluorouracil and leucovorin did not compromise the quality of life.
Conclusions: Weekly treatment with irinotecan plus fluorouracil and leucovorin is superior to a widely used regimen of fluorouracil and leucovorin for metastatic colorectal cancer in terms of progression-free survival and overall survival.
Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia
Background: Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil. We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia.
Methods: Between 1990 and 1994, we randomly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments: fludarabine (25 mg per square meter of body- ; surface area, administered intravenously daily for 5 days every 28 days), chlorambucil (40 mg per square meter, given orally every 28 days), or fludarabine (20 j mg per square meter per day for 5 days every 28 days) plus chlorambucil (20 mg per square meter t every 28 days). Patients with an additional response 1 at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles.
Results: Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone. Among the other two groups, the response rate was significantly higher for fludarabine alone than for chlorambucil alone. Among 170 patients treated with fludarabine, 20 percent had a complete remission, and 43 percent had a partial remission. The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent (P< 0.001 for both comparisons). The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons). The median overall survival among patients treated with fludarabine was 66 months, which was not significantly different from the overall survival in the other two groups (56 months with chlorambucil and 55 months with combined treatment). Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens.
Conclusions: When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil; overall survival is not enhanced.
Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group
To determine prognostic factors and treatment outcome, patients with primary progressive Hodgkin lymphoma (HD) registered in the database of the German Hodgkin Lymphoma Study Group (GHSG) were analyzed retrospectively. Detailed records from randomized prospective multicenter trials performed between 1988 and 1998 of 3807 patients recruited in these trials were reviewed. The median age of the 206 patients available was 34 years (range, 16-71). Fifty-seven patients (28%) in intermediate stage and 149 patients (72%) in advanced stage developed progressive disease (PD). One hundred and fifty-three patients (74%) were treated with salvage chemotherapy, 47 patients (23%) with salvage radiotherapy, and 6 patients (3%) did not receive any therapy due to rapid PD. Seventy patients (34%) were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation. The 5-year freedom from second failure (FF2F) and overall survival (OS) for all patients were 17% and 26%, respectively. The 5-year FF2F and OS for patients treated with HDCT were 31% and 43%, respectively. In multivariate analysis low Karnofsky performance score at the time of progression (P < .0001), age above 50 years (P = .019), and failure to attain a temporary remission on first-line treatment (P = .0003) were significant adverse prognostic factors for OS. Patients with none of these risk factors had a 5-year OS of 55% compared with 0% for patients with all 3 of these unfavorable prognostic factors. Although HDCT is a reasonable option for selected patients with primary progressive HD, the majority did not receive HDCT. Interestingly, salvage radiotherapy gave promising resuits-in Patients with localized PD.
Locoregional Recurrence Patterns After Mastectomy and Doxorubicin-Based Chemotherapy: Implications for Postoperative Irradiation
Purpose: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation.
Patients and Methods: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 1 16 months. Rates of isolated and total LRR (± distant metastasis) were calculated by Kaplan-Meier analysis.
Results: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21 %, and 22% for patients with zero, one to three, four to nine, or >= 10 involved nodes, respectively (P < .0001). Chest wall (68%) and supraclavicular nodes (41 %) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >= 10 nodes examined (24% v 11 %; P = .02). Patients with tumor size greater than 4.0 cm or extranodal extension >= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression.
Conclusion: Patients with tumors >= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.
Survival Benefit of High-Dose Therapy in Poor-Risk Aggressive Non-Hodgkin's Lymphoma: Final Analysis of the Prospective LNH87-2 Protocol-A Groupe d’Etude des Lymphomes de L'Adulte Study
Purpose: To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin’s lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index.
Patients and Methods: Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm.
Results: Among these 451 higher risk patients, 277 (61 %) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT was superior to sequential chemotherapy, with 8-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P = .02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P = .04; relative risk, 1.51).
Conclusion: On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment.
Utility of Positron Emission Tomography for the Staging of Patients With Potentially Operable Esophageal Carcinoma
Purpose: A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities.
Patients and Methods: Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS).
Results: FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P = .004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 1 1 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81 %, respectively; P = .027), but the specificity may have been higher (89% v 67%, respectively; P = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P = .025) and a similar sensitivity (46% v 43%, respectively; P = NS).
Conclusion: PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.
Epstein-Barr Virus Infection Is Predictive of CNS Involvement in Systemic AIDS-Related Non-Hodgkin's Lymphomas
Purpose: This study aimed at correlating EpsteinBarr virus (EBV) infection of systemic AIDS-related nonHodgkin lymphomas (AIDS-NHL) with the development of a CNS localization of the tumor.
Patients and Methods: Demographic, epidemiologic, clinical, histologic, and virologic features were collected for all systemic AIDS-NHL patients included in the study (n = 50). Pathologic specimens were classified according to the working formulation for NHL and the Revised European-American Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV small encoded RNA in situ hybridization; EBV-DNA detection in CSF was carried out by nested polymerase chain reaction using Epstein-Barr nuclear antigen-1specific primers. In addition, selected EBV-positive lymphomas were subjected to a detailed characterization of EBV molecular heterogeneity.
Results: Eleven patients had a CNS involvement at some point during their clinical history (four at diagnosis and seven at relapse). Thirty patients (11 with CNS involvement and 19 without) harbored EBV infection of the tumor. Sensitivity, specificity, and positive and negative predictive values of EBV-DNA detection in CSF for CNS involvement by lymphoma were 90%, 100%, 100%, and 97.6%, respectively. Factors significantly predictive of CNS involvement were EBV infection of the tumor (P = .003), an extranodal disease at diagnosis other than CNS (P = .006), and a non-CNS relapse (P = .O1). In four cases of CNS involvement, EBV-DNA in CSF preceded any other sign of disease by a mean of 35 days.
Conclusion: These results show that EBV infection of the tumor clone significantly increases the risk of CNS involvement by systemic AIDS-NHL, without regard of specific molecular features. The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with higher risk of CNS involvement and, therefore, may prove useful in the therapeutic stratification of these tumors.
Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations
Purpose: Recent laboratory data suggest a role for BRCA 1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from 13RCA 1/2 mutation carriers. Thus the goals of this study were to compare rates of. radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA112 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease.
Patients and Methods: Seventy-one women with a BRCA 1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence.
Results: Tumors from women in the genetic cohort were associated with high histologic (P = .0004) and nuclear (P = .009) grade and negative estrogen (P = .0001) and progesterone (P = .002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91 %, 80%, and 96%, respectively, for the sporadic cohort (P = not significant).
Conclusion: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA 1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA112 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.
Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy-A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group
Purpose: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.
Patients and Methods: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m2 was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.
Results: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P < .001). Time to progression in the brain was longer in the combined-modality group (P = .005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combinedmodality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P = .087).
Conclusion: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.
Prospective Trial of the Herbal Supplement PC-SPES in Patients With Progressive Prostate Cancer
Purpose: PC-SPES is an herbal supplement for which there are anecdotal reports of anti-prostate cancer activity. This phase II study was undertaken to assess the efficacy and toxicity of PC-SPES in prostate cancer patients.
Patients and Methods: Thirty-three patients with androgen-dependent prostate cancer (ADPCa) and 37 patients with androgen-independent prostate cancer (AIPCa) were treated with PC-SPES at a dose of nine capsules daily. Clinical outcome was assessed with serial serum prostate-specific androgen (PSA) level measurement and imaging studies.
Results: One hundred percent of ADPCa patients experienced a PSA decline of >= 80%, with a median duration of 57+ weeks. No patient has developed PSA progression. Thirty-one patients (97%) had declines of testosterone to the anorchid range. Two ADPCa patients had positive bone scans; both improved. One patient with a bladder mass measurable on computed tomography scan experienced disappearance of this mass. Nineteen (54%) of 35 AIPCa patients had a PSA decline of >=50%, including eight (50%) of 16 patients who had received prior ketoconazole therapy. Median time to PSA progression was 16 weeks (range, 2 to 69+ weeks). Of 25 patients with positive bone scans, two had improvement, seven had stable disease, 11 had progressive disease, and five did not have a repeat bone scan because of PSA progression. Severe toxicities included thromboembolic events (n = 3) and allergic reactions (n = 3). Other frequent toxicities included gynecomastia/gynecodynia, leg cramps, and grade 1 or 2 diarrhea.
Conclusion: PC-SPES seems to have activity in the treatment of both ADPCa and AIPCa and has acceptable toxicity. Further study is required to determine whether its effects exceed those expected with estrogen therapy.
Anastrozole Versus Tamoxifen as First-Line Therapy for Advanced Breast Cancer in 668 Postmenopausal Women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study
Purpose: To compare the efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) with that of tamoxifen as first-line therapy for advanced breast cancer (ABC) in postmenopausal women.
Patients and Methods: This randomized, doubleblind, multicenter study evaluated the efficacy of anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with tumors that were hormone receptor-positive or of unknown receptor status who were eligible for endocrine therapy. The primary end points were time to progression (TTP), objective response (OR), and tolerability.
Results: A total of 668 patients (340 in the anastrozole arm and 328 in the tamoxifen arm) were randomized to treatment and followed-up for a median of 19 months. Median TTP was similar for both treatments (8.2 months in patients who received anastrozole and 8.3 months in patients who received tamoxifen). The tamoxifen:anastrozole hazards ratio was 0.99 (lower one-sided 95% confidence limit, 0.86), demonstrating that anastrozole was at least equivalent to tamoxifen. Anastrozole was also as effective as tamoxifen in terms of OR (32.9% of anastrozole and 32.6% of tamoxifen patients achieved a complete response [CR] or partial response [PR]). Clinical benefit (CR + PR + stabilization of > 24 weeks) rates were 56.2% and 55.5% for patients receiving anastrozole and tamoxifen, respectively. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen (4.8% v 7.3% [thromboembolic events] and 1.2% v 2.4% [vaginal bleeding], respectively).
Conclusion: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Together with the lower observed incidence of thromboembolic events and vaginal bleeding, these findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with ABC.
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Revista Brasileira de Cancerologia - Volume 47 n°3 Jul/Ago/Set 2001