PURPOSE:To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS:Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS:Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION:The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Objectives. A SWOG/GOG phase 3 trial exploring the impact of 12-monthly cycles of paclitaxel given to patients with advanced ovarian cancer who achieved a complete response to primary chemotherapy was discontinued by the Data Safety and Monitoring Committee when a prospectively defined interim analysis revealed a highly statistically significant improvement in progression-free survival (PFS). At study closure, it was too early to assess the impact on overall survival.Methods. Patients (n = 296) received either 3 or 12 monthly cycles of paclitaxel (175 mg/m(2) over 3 h).Results. Of the 146 patients on the 3-cycle arm, 9 (6%) received > 3 cycles. Median ( 12 versus 3 cycles; intention-to-treat analysis) updated PFS (all pts) 22 versus 14 months, p = 0.006: overall survival (all pts) 53 versus 48 months, p = 0.34.Conclusion. Twelve cycles of single agent maintenance paclitaxel significantly improves PFS. Explanations for the lack of a favorable influence on overall Survival include: (a) treatment at relapse equalized outcome; (b) the sample size was insufficient to reveal a difference; (c) "crossover" of patients from 3 cycles to longer treatment masked a potential difference. An ongoing phase 3 trial will hopefully provide a definitive answer to the question of the impact of this maintenance strategy on overall Survival. (C) 2009 Elsevier Inc. All rights reserved.

Objective. While primary cisplatin-based intraperitoneal chemotherapy has been shown to favorably impact survival in small-volume residual advanced ovarian cancer, there is a need to develop strategies that improve the effectiveness of this approach.Methods. A multi-center phase 2 trial was conducted that added intravenous pegylated liposomal doxorubicin (day 8; 30-40 mg/m(2)) to a regimen of intraperitoneal cisplatin (day 2: 75 mg/m(2)) and intravenous (day 1; 135 mg/m(2)) plus intraperitoneal (day 8; 60 mg/m(2)) paclitaxel. Treatment was initially delivered on an every 3-week schedule, but was modified to an every 4-week program due to excessive toxicity. Patients were to receive 6 cycles of this regimen.Results. Of 68 patients entering this trial, 63 patients were eligible and evaluable, of whom 39 (62%) completed 6 cycles. Overall, 32 (51%) experienced at least 1 grade 4 or worse toxicity (most commonly hematologic) including 5 treatment-related deaths. Median progression-free survival (PFS) was 25 months (2-year PFS: 52%) and median overall survival 51 months, an outcome similar to previous reports of cisplatin-based intraperitoneal chemotherapy in comparable patient populations. Seventeen patients (27% of all eligible patients) were without evidence of disease recurrence >4 years following entry into the trial.Conclusion. Both the overall trial outcome, and specifically the excessively severe systemic toxicity of this regimen would prevent its future development in this exact form. The provocative PFS in a subset of individuals should encourage the development of alternative strategies designed to optimize the delivery of regional therapy in ovarian cancer management. (C) 2009 Elsevier Inc. All rights reserved.

5551 Background: There is a continuing debate over the role of combination, platinum-based chemotherapy for PS, recurrent ovarian cancer (OC). Although this phase 3 trial was closed prematurely by the SWOG Data Safety and Monitoring Committee (DSMC) due to slow patient accrual, it provided provocative results nonetheless. Methods: Patients with recurrent stage III or IV OC, with a progression-free and platinum-free interval of 6- 24 months after completion of first-line platinum-based chemotherapy, and up to 12 courses of non-platinum containing chemotherapy or biologic therapy as consolidation treatment after the first-line regimen were eligible and observed for progression-free survival (PFS) and overall survival (OS). Patients were randomized to either IV PLD (30 mg/m 2 ) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin (AUC=5mg/ML × min) once every four weeks alone. Results: The PLD arm enrolled 31 patients and the carboplatin alone arm enrolled 30 for a total of 61 patients out of the 900 planned. The response rates were 67% (18/27) for the PLD arm and 32% (9/28) for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS on the PLD arm was 12 months and 8 months on the carboplatin only arm. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). 26% of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusions: Although this study was closed early, because of slow patient accrual the results for the PLD arm are intriguing for response rates, median progression-free survival and overall survival. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent disease. No significant financial relationships to disclose.

Objective. Intraperitoneal (IP) chemotherapy Prolongs survival in optimally reduced Ovarian cancer patients. For patients in whom optimal debulking cannot be achieved, one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy. We Sought to evaluate overall Survival (OS), progression-free survival (PFS), percent of patients optimally debulked and toxicity in patients treated with this strategy.Methods. Women with adenocarcinoma by biopsy or cytology with stage III/IV (pleural effusions only) epithelial ovarian, fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous (IV) paclitaxel 175 mg/m(2) and carboplatin AUC 6 q 21 days x 3 cycles followed by Surgery (if >= 50% decrease in CA125). If optimally debulked they received IV paclitaxel 175 mg/m(2) and IP carboplatin AUC 5 (day 1) and IP paclitaxel 60 mg/m2 (day 8) q 28 days x 6 cycles.Results. Sixty-two patients were registered. Four were ineligible. Fifty-six were evaluated for neoadjuvant chemotherapy toxicities. One patient died of pneumonia. Five patients had grade 4 toxicity, including neutropenia (3), anemia, leukopenia, anorexia, fatigue, muscle weakness, respiratory infection, and cardiac ischemia. Thirty-six patients had debulking surgery. Two had grade 4 hemorrhage. Twenty-six patients received post-cytoreduction chemotherapy. Four had grade 4 neutropenia. At a median follow-up of 21 months, median PFS is 21 months and median OS is 32 months for all 58 patients. PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively.Conclusions. These results compare favorably with other studies of sub-optimally debulked patients. (C) 2008 Elsevier Inc. All rights reserved.

Platinum-resistant ovarian cancer continues to be a difficult therapeutic problem. Clearly, molecularly targeted agents should be evaluated in this patient population. Patients were eligible for this phase II study with stage III or IV ovarian cancer, whose tumor expressed Kit (CD117) or platelet-derived growth factor receptor (PDGFR) and with relapse of measurable disease within 6 months of completing frontline, platinum- and taxane-based chemotherapy. Patients were treated daily with 400 mg of imatinib mesylate orally. It was assumed that the agent would be of no further interest if the population response rate was less than 10%. A two-stage design was used for patient accrual. A total of 34 patients were registered to the study. Of these, 15 were found to be ineligible or not evaluable (8 because their tumor samples were negative for both DC117 and PDGFR). Of 19 evaluable patients, 2 (11%) tested positively for c-Kit and 17 (89%) tested positively for PDGFR. There were no objective responders. Thirteen patients (68%) had increasing disease or symptomatic deterioration, and six (32%) went off protocol during the first month due to adverse events. Median progression-free survival was 2 months (95% CI 1–3 months) and median overall survival was 10 months (95% CI 6–18 months). Eleven percent of patients experienced grade 4 hematologic/metabolic toxicity and 37% experienced grade 3 nonhematologic toxicity. We conclude that imatinib mesylate as a single agent does not appear to have useful clinical activity in c-Kit and/or PDGFR positive, recurrent ovarian cancer in heavily pretreated patients with ovarian cancer

PURPOSE:A previous report suggested the nadir serum CA-125 level within the group of patients with ovarian cancer who achieved normalization of CA-125 accurately defined the risk of relapse. Using similar CA-125 subgroups, we sought to determine if the baseline CA-125 level before initiation of maintenance chemotherapy in women achieving a clinically-defined complete response to primary chemotherapy would be of prognostic value.PATIENTS AND METHODS:Patients included in this retrospective analysis had been treated on one of two previously reported trials of maintenance chemotherapy (three v 12-monthly cycles of paclitaxel; oral altretamine), with a baseline CA-125 level of < or = 35 u/mL. Progression-free survival (PFS) from study entry was analyzed by the Cox regression model.RESULTS:The distribution of premaintenance baseline CA-125 levels for the 384 patients was 58%, 34%, and 8% for values of (A) < or = 10 u/mL, (B) 11 to 20 u/mL, and (C) 21 to 35 u/mL, respectively. The baseline CA-125 was highly statistically significant, either as a categoric variable (P < .001) or as a continuous variable (P < .0001). Median PFS was 24 months, 17 months, and 7 months for groups (A), (B), and (C), respectively. There was no evidence the CA-125 effect differed by trial or treatment in an interaction analysis (P = .70).CONCLUSION:The baseline CA-125 level before initiation of maintenance chemotherapy strongly predicts the risk of subsequent relapse. Patients with premaintenance baseline CA-125 values < or = 10 u/mL have a superior PFS compared with higher levels in the normal CA-125 range.

The objective of this study was to determine objective response and overall survival (OS) and progression-free survival (PFS) following cisplatin plus tirapazamine treatment in eligible consenting patients with metastatic or recurrent squamous or adenosquamous carcinoma of the cervix. Treatment consisted of intravenous tirapazamine, 260 mg/m2, followed by cisplatin, 75 mg/m2, every 21 days for six cycles. Of 56 registered cases, 52 were evaluable for toxicity. There were six grade 4 toxicities (anemia [three], dyspnea [one], neutropenia/granulocytopenia [one], and dehydration [one]). Fifty-three patients were evaluable for response, OS, and PFS. The 6-month OS rate was 56.6% (95% CI 43.3–69.9%). The objective response rate was 32.1% (4 complete [2 confirmed and 2 unconfirmed] and 13 partial [8 confirmed and 5 unconfirmed]). Higher response rates (16/34 [47.1%] vs 1/19 [5.3%], P = 0.0018) were observed in patients who had not previously received radiation-sensitizing chemotherapy, as were OS and PFS (13.9 vs 4.0 months, P < 0.0001; 5.3 vs 1.8 months, P = 0.01). The OS was considered too low to warrant further testing in this disease setting. Despite this, tirapazamine plus cisplatin was active in patients who had not received cisplatin previously. Prior use of radiosensitizing chemotherapy impacted response and survival significantly and should be considered in future clinical trials.

OBJECTIVE:The relationship between survival and early changes in the serum level of the CA-125 antigen in patients with advanced ovarian cancer remains poorly defined. METHODS:To explore this issue, the serum CA-125 values from 101 patients with advanced ovarian cancer who participated in a Southwest Oncology Group trial (SWOG 8412), which compared the systemic delivery of cisplatin/cyclophosphamide vs. carboplatin/cyclophosphamide (both delivered every 28 days for 6 cycles) in suboptimal residual stage III and IV ovarian cancer, were evaluated. All patients in this analysis had CA-125 values available for at least 8 weeks following initiation of chemotherapy. Cox proportional hazards regression was used in multivariate analysis to determine the prognostic significance of the CA-125 concentration. RESULTS:While pretreatment CA-125 values did not correlate with survival, the concentration of this tumor marker 8 weeks after initiation of therapy was a powerful independent prognostic factor. The median survivals for patients (n = 51) with a CA-125 < 35 U/ml, vs. patients (n = 50) with a CA-125 > 35 U/ml, at this time point, were 26 months and 15 months, respectively (P = 0.0001). Further, women with serum CA-125 values <50% of their pretreatment concentration at 8 weeks experienced a median survival of 21 months, compared to only 10 months for individuals with tumor marker levels >50% of their baseline value (P = 0.0003). CONCLUSION:Reduction in the serum CA-125 concentration over the initial two cycles of platinum-based chemotherapy is a powerful independent predictor of survival for patients with suboptimal stage III or IV ovarian cancer. Patients without significant declines in CA-125 after two cycles of platinum-based chemotherapy have a particularly poor prognosis.

Objective. Despite the improvement in progression-free and overall Survival in patients with advanced ovarian cancer associated with platinum-taxane chemotherapy, strategies are needed to prevent the greater than 70% recurrence rate.Method. The Southwest Oncology Group (SWOG) initiated a phase III intergroup trial of alpha-interferon (IFN alpha-26, Schering-Plough, Kenilworth, NJ) in weekly closes of 50 x 10(6) IU (for 6 doses) versus observation only in patients with no pathological evidence of residual disease at second-look Surgery in 1988.Results. Patient accrual was extremely slow and the trial was permanently closed in 1999 by the SWOG Data and Safety Monitoring Committee with 74 registered patients. Of these patients, 70 were evaluable for progression-free and overall Survival. There was no significant difference between the two study arms in relation to median progression-free survival (P = 0.56). The median survival duration associated with intraperitoneal alpha-interferon had not been reached versus 87 months on the observation arm. In general, intraperitoneal alpha-interferon vas well tolerated. There were no treatment-related deaths or grade 4 adverse events. Although no efficacy conclusions can be drawn from this prematurely Closed trial, it should be noted that 57% of the patients on the observation arm recurred and all died, whereas 63% recurred and only 43% died on the intraperitoneal alpha-interferon arm.Conclusion. Although this was a negative Study, there should Continue to be interest in the use of biological therapy to improve survival of patients in complete remission following primary chemotherapy. (c) 2005 Elsevier Inc. All rights reserved.

Objectives. To evaluate the response rate and progression free and overall survival of patients with advanced endometrial cancer treated with paclitaxel, carboplatin and amifostine. To evaluate the toxicity of amifostine when used in combination with carboplatin and paclitaxel.Methods. Forty-seven eligible patients (median age: 66; range 45-82) with bidimensionally measurable advanced, recurrent, or refractory endometrial cancer were treated with carboplatin (AUC = 6), paclitaxel (175 mg/M2) and amifostine (740 mg/M2) every 4 weeks for 6 cycles or until disease progression or unacceptable toxicity.Results. There were 4 CRs (8%) (2 confirmed, 2 unconfirmed) and 15 PRs (32%) (1) confirmed, 6 unconfirmed) for a total response rate of 40% (95% confidence interval [CI], 26% to 56%). The median progression-free survival (PFS) was 7 months (95% Cl, 6-9 months) and a 6-month PFS rate of 64% (95% Cl, 50% to 78%). The median overall survival was 14 months (95% Cl, 12 to 17 months). Toxicity was tolerable. While 79% of patients developed Grade 3/4 neutropenia, (30% Grade 3, 49% Grade 4), there were no episodes of Grade 4 febrile neutropenia and one episode of infection with grades 3-4 neutropenia.Conclusion. The combination of paclitaxel and carboplatin with amifostine was well reasonably tolerated in this cohort. The regimen demonstrated significant activity in endometrial cancer, comparable to other multi-agent chemotherapy programs in terms of response rate and survival, and with a favorable toxicity profile. (c) 2004 Elsevier Inc. All rights reserved.

5013 Background: Patients (pts) with AOC who achieve a CCR have a high risk of recurrence. Reliable methods to identify the risk of relapse may lead to modifications in disease management. Methods: Crawford, et al. (Proc ASCO 2004: 23:448) showed that AOC pts with a nadir CA-125 level of ≤ 10 experienced substantially improved 2-year progression-free survival (PFS), compared to pts whose CA-125 ranged from 11–20 or 21–30. Using these criteria but with entry CA-125, we analyzed the risk of progression in pts treated on 2 trials of “maintenance therapy” (MT) in women with AOC who attained a CCR following primary chemotherapy (CT): (1) phase 2 SWOG trial of altretamine (260 mg/m2 daily x 14 days, repeated monthly x 6 months (m)) (n=97); (2) phase 3 SWOG/GOG trial of paclitaxel (175 mg/m2 over 3 hours for 3 or 12 m) (n=287). Pts must enter the trials no later than 8 weeks after the last dose of prior CT. Pretreatment CA-125 was ≤ 35 for all pts. PFS from study entry was analyzed by the Cox regression model stratifying by trial/treatment and adjusting for optimal stage III vs. suboptimal stage III or stage IV disease at diagnosis and age (≤ 65 vs. > 65). Results: The distribution of pretreatment CA-125 for the 384 pts was 58%, 34% and 8% for values (a) ≤ 10, (b) >10–20, (b) >20–35 respectively. 280 pts had progressed at the time of analysis, approximately 25% by CA-125 progression criteria (Vergote, et al. JNCI 2000; 92:1534–1535). CA-125 was highly statistically significant either as a categorical variable as described above (p<0.0001), or as a continuous variable (p<0.0001). Median PFS was 24, 17 and 7 m, respectively, for groups (a), (b), and (c). There was no evidence the CA-125 effect differed by trial or treatment in an interaction analysis. Conclusions: The CA-125 level at the initiation of “MT” in women with AOC who attain a CCR to primary chemotherapy strongly predicts the risk of subsequent relapse. Patients with pretreatment CA-125≤ 10 have superior PFS. No significant financial relationships to disclose.

Objective This report provides follow-up progression-free survival (PFS) and median survival data for women who achieved clinical complete remission (cCR) from stage III ovarian cancer after first-line therapy and were treated with altretamine consolidation therapy. Methods Patients who enrolled in the SWOG 9326 study from September 1993 to July 1997 were required to have documented cCR from stage III ovarian cancer following front-line platinum-based therapy. Treatment consisted of 6 months of oral altretamine at 260 mg/m2/day for 14 consecutive days of a 28-day cycle. Results Ninety-seven of 112 enrolled patients were evaluable for efficacy. This report presents median 6.2-year follow-up, dating from study registration. Median PFS was 28 (95% CI: 19–43) months. Median PFS for patients with optimal disease was 45 (95% CI: 27–48) months and for patients with suboptimal disease was 17 (95% CI: 12–26) months. Twenty-six of 61 (43%) patients with optimally debulked lesions and 5 of 36 (14%) patients with suboptimally debulked lesions remained disease free. Median survival of patients with optimally debulked disease has not been reached; median survival of patients with suboptimally debulked disease was 39 (95% CI: 19–51) months. No treatment-related adverse events were reported during the follow-up period. Conclusions Consolidation therapy with oral altretamine was generally well tolerated and associated with prolonged progression-free and overall survival in the Phase II setting.

Objective. The survival of cervix cancer patients is associated with their hemoglobin (Hgb) level during radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase II trial to determine whether recombinant human erythropoietin (rHuEPO) safely corrects anemia during chemoradiotherapy for cervix cancer.Methods. Patients had stage IIB-IVA cervix cancer and a Hgb between 8.0 and 12.5 g/dl. All patients received rHuEPO thrice weekly and oral iron starting 10-15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin followed by intracavitary brachytherapy.Results. Fifty-three patients from 26 institutions received the protocol treatment. The mean Hgb was 10.4+/-1.3 g/dl on the first day of rHuEPO administration (baseline), 11.0+/-1.6 g/dl on the first day of chemoradiotherapy, 11.6+/-1.9 g/dl at the midpoint of chemoradiotherapy, and 11.8+/-2.2 g/dl at the end of chemoradiotherapy. The target Hgb level of 12.5 g/dl was achieved in 40% of patients (95% CI 26-56%) by the midpoint of chemoradiotherapy. Change in Hgb was associated with baseline serum iron (P=0.008) and transferrin saturation (P=0.05) levels, but not with baseline Hgb or serum ferritin, or patient age. Seven patients developed deep vein thrombosis. Two-year progression-free survival (PFS) was 43% and overall survival (OS) was 51%. Survival was significantly associated with Hgb level at the end of chemoradiotherapy, but not with the baseline Hgb level.Conclusions. rHuEPO and iron gradually increased Hgb levels in anemic women with local advanced cervix cancer during chemoradiotherapy. There was a higher than expected incidence of deep vein thrombosis. The progression-free and overall survival rates were lower than reported for women with normal Hgb levels. (C) 2004 Elsevier Inc. All rights reserved.

Objective. To retrospectively analyze data from a previously reported randomized trial of either pelvic radiation (RT) or RT + chemotherapy (CT) in patients undergoing radical hysterectomy and pelvic lymphadenectomy with positive pelvic lymph nodes, parametrial involvement, or surgical margins; to explore associations between RT + CT; and to investigate histopathologic and clinical factors which might be predictive of recurrence.Methods. Histopathologic sections from biopsies and hysterectomies and clinical data were reviewed from patients with stage IA2, III, or IIA cervical cancer treated with RT or RT + CT (cisplatin 70 mg/m(2) plus fluorouracil 1000 mg/m(2) every 3 weeks for four cycles). A univariate analysis was performed because the relatively small sample size limited the interpretation of a multivariate analysis.Results. Of the 268 enrolled women, 243 (RT = 116; RT + CT = 127) were evaluable. The beneficial effect of adjuvant CT was not strongly associated with patient age, histological type, or tumor grade. The prognostic significance of histological type, tumor size, number of positive nodes, and parametrial extension in the RT group was less apparent when CT was added. The absolute improvement in 5-year survival for adjuvant CT in patients with tumors <= 2 cm was only 5% (77% versus 82%), while for those with tumors > 2 cm it was 19% (58% versus 77%). Similarly, the absolute 5-year survival benefit was less evident among patients with one nodal metastasis (79% versus 83%) than when at least two nodes were positive (55% versus 75%).Conclusions. In this exploratory, hypothesis-generating analysis, adding CT to RT after radical hysterectomy, appears to provide a smaller absolute benefit when only one node is positive or when the tumor size is < 2 cm. Further study of the role of CT after radical hysterectomy in patients with a low risk of recurrence may be warranted. (c) 2004 Elsevier Inc. All rights reserved.

Objectives. To evaluate response rates, progression-free survival (PFS), overall survival (OS), and toxicity of two high-dose chemotherapy regimens with stem cell rescue used to treat patients with recurrent or persistent stage III/IV ovarian cancer, with the goal of taking one forward into a Phase III comparison with conventional therapy.Methods. Patients under 65 with clinically or pathologically persistent disease after initial chemotherapy or those relapsing >6 months after a complete remission (CR) were randomized to CMC carboplatin (1500 mg/m(2)), mitoxantrone (75 mg/m(2)), and cyclophosphamide (120 mg/kg)], or CTC: [cisplatin (165 mg/m(2)), thiotepa (600 mg/m(2)), and cyclophosphamide (5625 mg/m(2))] with stem cell rescue.Results. Of 67 randomized, the 32 and 26 eligible in the CMC and CTC arms were matched including age (median 49), maximum tumor diameter, and disease status at transplant. Low-risk disease (maximum diameter disease less than or equal to 0.5 cm and platinum sensitivity) was demonstrated in only approximately one-half of the patients. There were two treatment-related deaths in each arm. The median PFS was 13 and 8 months, respectively, for the CMC and CTC arms. The median OS was 29 and 22 months for the CMC and CTC arms. In a multivariate analysis of PFS, normal CA125 at transplant and CR to primary therapy were significant; for OS, normal CA125 and platinum sensitivity were significant.Conclusions. The CMC regimen was the superior regimen. However, few patients were long-term progression-free survivors. A clinical CR to primary therapy and a normal CA125, seen in a minority of patients, were requirements for a favorable outcome. (C) 2004 Elsevier Inc. All rights reserved.

Objectives. To assess the activity of vinorelbine in women with recurrent or resistant epithelial ovarian cancer following treatment with platinum and paclitaxel in terms of survival rate at 6 months, objective response rate (in the subset of patients with bidimensionally measurable disease), and health-related quality of life.Methods. Seventy-nine evaluable patients with progressive ovarian cancer following platinum and taxane therapy received vinorelbine 30 mg/m(2) days 1 and 8 of a 21-day treatment cycle.Results. Six-month survival rate for the entire group was 65% (95% CI: 54-75%) and median survival was 10.1 months (95% CI: 7.7-13.6 months). In the 71 women with measurable disease, 0 complete and 2 partial responses were observed (RR = 3%) (95% CI: 0.3-10%). Patients reported substantial symptom-related distress at baseline, which persisted, but did not worsen, during treatment. Patients also had impaired physical functioning at baseline and this continued to decline during treatment.Conclusions. The 6-month survival rate achieved with salvage vinorelbine is comparable to the results obtained with other salvage therapies in patients with relapsed ovarian cancer. During the initial 10 weeks of treatment, vinorelbine did not appear to be effective in alleviating the symptom-related distress or progressive impairment of physical functioning associated with this disease. (C) 2004 Elsevier Inc. All rights reserved.

PURPOSE:To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinically defined complete response to a platinum/paclitaxel-based chemotherapy could prolong subsequent progression-free survival (PFS) and affect ultimate survival.PATIENTS AND METHODS:Patients were randomly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival.RESULTS:As of September 6, 2001, 277 patients (262 assessable) had entered the trial, with a total of 54 PFS events having developed among 222 patients with follow-up data. With the exception of peripheral neuropathy, there were no major differences in toxicity between the regimens. The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms, respectively. One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis (for stratification factors) were.0035 and.0023, respectively, both in favor of the 12-cycle arm. The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 (99% confidence interval, 1.08 to 4.94). With a protocol-specified early termination boundary of P =.005, these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial. As of the date of study closure, there was no difference in overall survival between the treatment arms.CONCLUSION:Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinically defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS.

PURPOSE The median survival time for women with optimally debulked adenocarcinoma of the ovary treated with intravenous (IV) chemotherapy is 41 to 52 months, and the 2-year survival rate is 65% to 70%. Recent studies evaluating intraperitoneal (IP) chemotherapy have reported a median survival time of 49 to 63 months and 2-year survival rates of 70% to 80%. This phase II trial was undertaken to evaluate the feasibility of and 2-year survival rate achieved by the combination of IP paclitaxel, IP cisplatin, and IV paclitaxel in women with optimally debulked, stage III ovarian cancer. PATIENTS AND METHODS Treatment consisted of paclitaxel 135 mg/m(2) IV over 24 hours on days 1 to 2, cisplatin 100 mg/m(2) IP on day 2, and paclitaxel 60 mg/m(2) IP on day 8 administered every 21 days for six cycles. RESULTS In 68 assessable women with optimal stage III ovarian cancer, the 2-year survival rate was 91%, and the median survival time was 51 months. The 2-year disease-free survival rate was 66%, and median disease-free survival time was 33 months. Ninety-six percent of all patients experienced at least one grade 3 to 4 adverse event during therapy, with the most common events being neutropenia (79%), nausea (50%), vomiting (34%), and fatigue/malaise/lethargy (24%). Seventy-one percent of patients completed all six cycles of IV/IP therapy as planned. CONCLUSION Combined IV and IP chemotherapy with cisplatin and paclitaxel is associated with a very promising 2-year survival rate in women with optimally debulked ovarian cancer. The ultimate impact of this approach on overall survival requires further evaluation in a randomized trial setting.

Purpose : An association between expression of : two of five HLA class I antigens (HLA-A2, HLA-A28, HLA-B44, HLA-B45, and HLA-C3; collectively called M5) and response to an allogeneic melanoma vaccine (Melacine; Corixa Corporation, Seattle, WA) has been described in stage IV melanoma. This study investigated whether class I antigen expression impacted relapse-free survival (RFS) after adjuvant therapy with this vaccine.Patients and Methods: We performed class I (HLA-A, HLA-B, and HLA-C) serotyping on patients enrolled onto Southwest Oncology Group Trial 9035, a randomixed, observation-control led, phase III trial of adjuvant Melacine. All patients had clinically node-negative cutaneous melanoma (1.5 to 4.0 mm). Interactions between treatment and class I antigen expression were tested. Analyses involved all serotyped patients and were adjusted for tumor thickness, method of nodal staging, sex, ulceration, and primary tumor site.Results: HLA typing was performed on 553 (80%) of the 689 enrolled patients (294 vaccinated and 259 observed). Expression of greater than or equal to two M5 antigens was associated with a superior vaccine treatment effect. Among patients who matched greater than or equal to two of the MS, the 97 vaccine-treated patients had improved RFS compared with the 78 observation patients (5-year relapse-free survival, 83% v 59%; P = .0002). The major components of this effect were contributed by HLA-A2 and HLA-C3. Among those who were HLA-A2-positive and/or HLA-C3-positive, the 5-year RFS for vaccinated patients was 77%, compared with 64% for observation (P = .004). There was no impact of HLA-A2 and/or HLA-C3 expression among observation patients.Conclusion: This prospective analysis indicates a highly significant benefit of adjuvant therapy with Melacine among patients expressing greater than or equal to two of the M5 class I antigens, validating a prior observation in stage IV disease. HLA-A2 and HLA-C3 contributed most to this effect. Processed melanoma peptides found in Melacine may be presented by HLA-A2 and HLA-C3 and play a role in preventing relapse in vaccinated patients. c 2002 by American Society of Clinical Oncology.