Intraperitoneal interferon-alpha in residual ovarian carcinoma: a phase II gynecologic oncology group study.

OBJECTIVE: The purpose of this study was to confirm the activity of interferon-alpha intraperitoneally in minimal residual epithelial ovarian cancer in a Phase II multi-institutional trial and to investigate the activity of the agent based on prior response to first-line platinum compounds. METHODS: Ninety-two patients with minimal residual (<0.5 cm) epithelial ovarian cancer at reassessment laparotomy were entered into a multicenter trial of intraperitoneal interferon-alpha given for 12 cycles unless disease progression or unacceptable toxicity occurred first. Patients were considered favorable if they were platinum sensitive and/or relapsed 6 months or longer after completing treatment and unfavorable if they were platinum insensitive and/or relapsed shorter than 6 months after completing treatment and/or had stable or progressive disease during initial therapy. A third-look laparotomy was performed within 12 weeks of completion of treatment in those patients who were in clinical remission. RESULTS: Eighty patients were clinically evaluable for toxicity only (48 favorable, 32 unfavorable) and 46 of them were evaluable for response, of whom 25 were favorable (platinum sensitive) and 21 unfavorable (platinum resistant). In the favorable group, there was a 28% surgically documented response rate (7/25 patients): 16% (4/25) had complete responses (negative reassessment operation), 12% (3/25) had partial responses, 32% (8/25) were nonresponders, and 40% (10 patients) developed progressive disease before planned reassessment operation. In the unfavorable group, there were no responding patients: 6 were nonresponders at reassessment operation and 15 developed progressive disease before planned reassessment operation. Of the 80 patients evaluable for toxicity, the most common adverse effects that were more than grade 2 were gastrointestinal (12; 15%), fever (8; 10%), neutropenia (7;9%), and leukopenia (6; 8%). Grade 4 toxicity was seen in 5 patients; each had fever and gastrointestinal toxicity, and 1 each had neutropenia and thrombocytopenia. CONCLUSIONS: Interferon-alpha is an active and generally well-tolerated agent in favorable patients with minimal residual epithelial ovarian cancer at second-look surgery. These results are comparable to those achieved with cytotoxic chemotherapy. If Phase III trials are considered in the patients with minimal residual ovarian cancer, they should be limited to the platinum-sensitive patient population.     

Carcinosarcoma of the ovary treated with platinum and taxane: the memorial Sloan-Kettering Cancer Center experience

INTRODUCTION: Due to the rarity of ovarian carcinosarcomas, the optimal chemotherapeutic regimen to treat this aggressive disease is yet to be determined. The purpose of this study was to determine the response rate, recurrence-free survival, and overall survival of patients with ovarian carcinosarcoma who were treated with the combination of platinum and a taxane as first-line chemotherapy. METHODS: We identified all patients with ovarian carcinosarcoma who received a combination of platinum and taxane either after initial tumor resection or as neoadjuvant therapy. Data extracted from the medical records included residual tumor after surgery, number, type and dose of chemotherapy cycles, tumor response, and survival outcome. RESULTS: Between 1991 and 2005, 30 patients were identified for analysis. Twenty-four patients had stage III disease, 5 had stage IV disease, and 1 had stage II disease. All patients underwent surgical resection and 17 (57%) were cytoreduced to less than 1 cm. Twenty-eight patients received chemotherapy after surgery, and 2 patients received chemotherapy before surgery. Twenty-four patients (80%) received carboplatin and paclitaxel, 3 (10%) received carboplatin and docetaxel, and 3 (10%) received cisplatin and paclitaxel. Twelve (40%) had a complete response, 7 (23%) a partial response, 2 (7%) stable disease, and 9 (30%) progression of disease. The median time to progression for responders was 12 months. With a median follow-up of 23 months, the median overall survival was 43 months for survivors. The 3- and 5-year survival rates were 53% and 30%, respectively. CONCLUSION: The combination of platinum and a taxane is a viable first-line treatment option for patients with ovarian carcinosarcoma.     

Duration of second or greater complete clinical remission in ovarian cancer: exploring potential endpoints for clinical trials

OBJECTIVE: To explore benchmarks for future consolidation strategies, we evaluated a strictly defined (normal CA-125 and normal CT) second-complete-remission (CR) ovarian cancer population for 1) the median progression-free survival (PFS), 2) the frequency with which second remission exceeds first, and 3) the proportion of patients in remission at given time points. METHODS: Retrospective sampling was carried out at Memorial Sloan-Kettering (10/1993-12/2000) and the Royal Marsden Hospital (1/1995-4/2003) for the following: histological confirmation and elevated CA-125 at diagnosis; primary surgery; first-and second-line platinum-based chemotherapy with CR; and no maintenance therapy. RESULTS: In 35 patients 1) the duration of first PFS was 17.8 months (95% CI, 13.2-24.5 months) and second PFS was 10.8 months (95% CI, 9.6-12.2 months); 2) the number of patients with second response longer than first was 3/35 (9%); 3) the proportion of patients remaining in second complete remission was 100% (3 months), 100% (6 months), 83% (9 months), 34% (12 months), 23% (15 months) and 8.6% (18 months), respectively. CONCLUSION: 1) The median PFS from second complete remission is short. 2) A second response is rarely longer than the first even in this second CR population. 3) The number of patients with a second response longer than the first, or the proportion of patients remaining in complete remission at given time points could be evaluated as an outcome measure in future studies.     

Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study

OBJECTIVE: The purpose was to examine the outcomes of patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, with a special emphasis on the patients' quality of life (QOL). METHODS: Seventeen patients with advanced ovarian cancer were treated with neoadjuvant chemotherapy based on the extent of disease on computer tomography. All patients received combined platinum/paclitaxel chemotherapy. Debulking surgery was performed after three cycles or six cycles of chemotherapy, depending on the response to the chemotherapy. Patients' QOL was studied over time using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and was then compared with that of patients treated with conventional treatment in the previous cohort. RESULTS: The response rate to chemotherapy assessed at three cycles was 82.4%. The rate of optimum debulking to residual disease less than 2 cm after chemotherapy was 76.9%, and 38.5% had no gross residual disease after surgery. The median overall survival was 22.9 months. The median disease-free interval was 13.3 months. The overall QOL improved after chemotherapy and this continued to improve up to 12 months. The other functional scales also showed improvements over time, apart from the initial transient deterioration in the role functioning and cognitive functioning at 3 months after chemotherapy. Patients treated with neoadjuvant chemotherapy seem to have better but statistically insignificant difference in QOL parameters than patients treated conventionally. CONCLUSION: Neoadjuvant chemotherapy is an alternative treatment for patients with advanced ovarian cancer in whom the chance of optimal cytoreduction is low. The patients' overall quality of life and functional status improve after neoadjuvant chemotherapy.     

Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study

OBJECTIVE: To evaluate the activity of single agent weekly paclitaxel in patients with both platinum and paclitaxel (delivered every 3 weeks)-resistant ovarian cancer. METHODS: Forty-eight patients with platinum and paclitaxel-resistant ovarian cancer (defined as progression during, or recurrence < 6 months following, their prior treatment with both agents) received single agent weekly paclitaxel (80 mg/m2/week) until disease progression (assuming acceptable toxicity). Following the initial 12 weekly doses, treatment could be given for 3 weeks, with a 1 week break. RESULTS: In this chemoresistant population, the objective response rate was 20.9%. Serious adverse events were relatively uncommon (neuropathy-grade 2: 21%; grade 3: 4%; and grade 3 fatigue: 8%). CONCLUSION: The weekly administration of paclitaxel can be a useful management approach in women with both platinum and paclitaxel (given every 3 weeks)-resistant ovarian cancer. It would be appropriate to directly compare weekly to every 3-week paclitaxel delivery in the setting of primary chemotherapy of advanced ovarian cancer.     

Prognostic implications of large volume residual disease in patients with advanced stage epithelial ovarian cancer

Thirty-two patients with Stage III or IV epithelial ovarian cancer and residual tumor volumes in excess of 2 cm in diameter after initial debulking were treated with platinum and cyclophosphamide chemotherapy. Twenty-seven patients (84%) received at least six courses of chemotherapy. Six patients developed grade 3 or 4 hematologic toxicity and one patient died with granulocytopenia and sepsis. The actuarial survival of the total group of patients was 78% at 12 months, 27% at 24 months, and 11% at 36 month. Of patients with residual disease 2-4 cm in diameter, 82% were alive 12 months after diagnosis and 46% were alive at 24 months. In contrast, patients with greater than 4 cm residual disease had a 12-month survival of 73% and a 24-month survival of only 7%. The size of residual tumor after surgery remains a very important prognostic factor in patients treated with platinum-based combination chemotherapy. Reoperation with further tumor debulking should be considered in ovarian cancer patients referred for chemotherapy with large volume residual disease to maximize response to combination chemotherapy.     

Survival following the documentation of platinum and taxane resistance in ovarian cancer: a single institution experience involving multiple phase 2 clinical trials

OBJECTIVES: There are very limited data in the oncology literature regarding the survival of women with both platinum and taxane-refractory ovarian cancer. METHODS: To examine this issue, we retrospectively reviewed the survival of patients treated on one (or more) of four previously reported nonrandomized single-agent phase 2 trials (topotecan, liposomal doxorubicin, gemcitabine, docetaxel), involving women with well-characterized platinum/taxane-resistant ovarian, fallopian tube, and primary peritoneal cancers. Following their most recent treatment with both classes of agents, patients must have either not responded to therapy or experienced a treatment-free interval of <3 months before documented disease progression. RESULTS: The median survival of the 111 patients (median age 61) included in this analysis was 6 months (range 1-37 months). Whereas 36 patients (32%) survived for <4 months, 30 patients (27%) lived for > or =12 months following documentation of resistance to both platinum and taxane therapy. CONCLUSION: With currently available antineoplastic drug therapy of platinum/taxane-resistant ovarian cancer, overall survival is relatively short, but a substantial minority of patients can be anticipated to live for periods in excess of 1 year. It remains uncertain whether such unexpectedly prolonged survival results from a biological response to chemotherapy or simply reflects the natural history of disease in a subset of patients with this malignancy.     

Long term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy

Abstract. Epenetos AA, Hird V, Lambert H, Mason P, Coulter C. Long term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy.
Purpose: To determine the long term survival of patients with advanced ovarian cancer treated with radioimmunotherapy following cytoreductive surgery and platinum based chemotherapy.
Patients and Methods: Eligibility criteria included patients with histological evidence of ovarian cancer stages IC-IV following completion of conventional platinum containing chemotherapy. Of 52 patients entered into the study, 31 had residual disease following standard chemotherapy and 21 patients had achieved complete remission. Treatment consisted of one intraperitoneal administration of 25 mg of monoclonal antibody HMFG1 labelled with 18 mCi/m² of ⁹⁰Y. Survival was the primary end-point.
Results: In the group of 21 patients who had achieved complete remission following surgery, conventional chemotherapy and intraperitoneal radioimmunotherapy, the median survival has not been reached with a maximum follow-up of 12 years. Survival at greater than 10 years is 78%.
Conclusion: This study suggests that a substantial proportion of patients who achieve complete remission with conventional therapy can achieve a long-term survival benefit when treated with intraperitoneal radioimmunotherapy using HMFG1 labelled with ⁹⁰Y.     

Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study

OBJECTIVE: To evaluate the activity of oral Altretamine in women with epithelial ovarian carcinoma who responded (PR or CR) to first line chemotherapy but relapsed within 6 months. The protocol was later amended to include patients with relapse within 12 months. METHODS: A multicentric phase II trial. The patients had to have measurable disease. No more than one prior chemotherapy regiment was allowed. The patients were treated with 260 mg/m(2)/day of Altretamine in four divided doses for 2 weeks, repeated every 4 weeks. The response was evaluated after every two courses. RESULTS: Thirty-one eligible patients were treated with a median of 3 courses of Altretamine (range 1-12). Hematological toxicity was minimal. Gastrointestinal toxicity was common. Response evaluation was possible for 26 patients. Three patients (9.7% intent-to-treat) achieved a partial response. Eight patients had stable disease, and 15 patients had progressive disease after two treatment courses. The median time to progression was 10 weeks (range, 5-51 weeks). Medial survival was 34 weeks (range, 7-112+). CONCLUSION: Altretamine should not be chosen as standard treatment in patients with platinum-resistant recurrent ovarian cancer. However, Altretamine represents a useful alternative in patients who prefer oral treatment or when socioeconomic considerations are an important issue.     

The role of topotecan as second-line therapy in patients with recurrent ovarian cancer

INTRODUCTION: Up to 80% of patients with advanced ovarian cancer will recur following first-line platinum containing chemotherapy. Topotecan has recently been used as a second-line agent in treatment of advanced ovarian disease. The aim of the study was to evaluate the effect of topotecan on response rate and progression-free interval on patients with recurrent ovarian cancer who had been treated with platinum-containing first-line chemotherapy. METHODS: A retrospective review of all cases of recurrent ovarian cancer treated with topotecan was done. Response was determined using radiologic reports (CT scans, ultrasound scans), CA-125 level and the clinical evaluation. Response type was determined using World Health Organization (WHO) criteria. RESULTS: Between 1998-2000, a total of 43 patients were treated with topotecan. Median age was 57 (range 41-80), 40/43 patients had stage III and IV, 37/43 patients had Grade 3 tumors. Seventeen of 43 patients (39.5%) demonstrated stable disease and 9/43 (21%) patients demonstrated partial response. Median time to response was eight weeks, median progression-free interval was 31 weeks and median time of follow-up and survival was 48 weeks. CONCLUSION: Topotecan is considered a reasonable option for treatment of patients with recurrent ovarian cancer that have failed previous treatment with platinum-containing chemotherapy.     

白蛋白结合型紫杉醇联合铂类或异环磷酰胺治疗复发性卵巢癌的疗效及安全性分析

目的:观察白蛋白结合型紫杉醇联合铂类或异环磷酰胺治疗复发性卵巢癌的临床疗效及毒副反应。方法:回顾分析我院46例复发性卵巢癌患者接受含不同制剂紫杉醇的联合化疗的疗效及安全性。26例铂敏感复发患者分别采用白蛋白结合型紫杉醇或溶剂型紫杉醇联合铂类化疗,20例铂耐药复发患者采用白蛋白结合型紫杉醇或溶剂型紫杉醇联合异环磷酰胺方案,每21天为1疗程,直至完全缓解后再巩固2个疗程或疾病进展或出现不可耐受的不良反应。比较患者间临床效果、毒副作用及预后差异。结果:铂敏感复发患者中,白蛋白结合型紫杉醇组的完全缓解率显著高于溶剂型紫杉醇组(60%vs 18.8%,P0.05);两组的客观缓解率分别为90%、75%。铂耐药复发患者中,白蛋白结合型紫杉醇组的完全缓解率显著高于溶剂型紫杉醇组(16.7%vs 0%,P0.05);两组的客观缓解率分别为66.7%、57.1%。铂敏感复发患者中,白蛋白结合型紫杉醇组及溶剂型紫杉醇组的中位无进展生存时间(PFS)分别为10.25、7.5个月(P0.05);铂耐药复发患者中白蛋白结合型紫杉醇组及溶剂型紫杉醇组的中位PFS分别为7.8、5.6个月(P0.05)。4组患者的不良反应主要表现为骨髓抑制和胃肠道反应,铂敏感、铂耐药患者中白蛋白结合型紫杉醇组及溶剂型紫杉醇组各种严重不良反应的发生率均无显著差异。结论:与溶剂型紫杉醇比较,含有白蛋白结合型紫杉醇的联合化疗方案治疗铂敏感或铂耐药复发性卵巢癌均有更高的完全缓解率,可有效延长PFS,且不额外增加严重毒副反应的发生率。     

An analysis of surgical versus chemotherapeutic intervention for the management of intestinal obstruction in advanced ovarian cancer

The objective of this study was to compare the treatment outcomes of surgical versus chemotherapeutic interventions for the management of intestinal obstruction secondary to metastatic epithelial ovarian cancer. A retrospective analysis of 39 patients with epithelial ovarian cancer who had 98 events of intestinal obstruction was performed. A medical records review of patients treated for advanced ovarian cancer from 1973 to 2003 was conducted. Time from treatment to obstruction, complications, and predictors of outcome were analyzed. Mean time from diagnosis of cancer to first obstruction was 38 months (range, 7-234 months). Of 39 patients with obstruction, 5% were stage I, 2% stage II, 85% stage III, and 8% stage IV. Prior to first obstruction, the median number of prior surgeries was 2 and chemotherapy regimens 3. Sites of the 98 events of obstruction were small intestine, 79 (81%); large intestine, 8 (8%); and combined small and large intestines, 11 (11%). The mean time to re-obstruction was 6.4 months (0-24) for chemotherapy, 5.1 months (0-40) for surgery, and 1.9 months (0-15) for supportive care. The mean hospital stays were 7 days (2-10) for chemotherapy, 18 days (3-50) for surgery, and 7 days (0-20) for supportive care. There were 4 major complications in the chemotherapy patients, 11 in the surgical patients, and 2 in the supportive only patients. The only significant factor predictive of > or =6 month obstruction-free period was prior response to platinum-based chemotherapy. Of the 13 patients with a response to chemotherapeutic or surgical treatment, 46% had an initial response to platinum-based chemotherapy, while 27% of 22 patients who re-obstructed in <6 months were platinum sensitive. In this retrospective analysis of selected patients, surgery and chemotherapy were found to have similar outcomes. The surgical approach had higher morbidity. The best predictor of either treatment's effectiveness is tumor sensitivity to platinum-based chemotherapeutic agents (P= 0.168).     

Phase II evaluation of a 3-day infusion of topotecan in patients with recurrent ovarian or primary peritoneal cancer

OBJECTIVE: To assess the efficacy and toxicity profile in patients treated with topotecan at 2.0 mg/m2/day x 3 days every 3 weeks. MATERIALS AND METHODS: Eligibility criteria included patients with recurrent primary peritoneal or epithelial ovarian cancer with > or =6 months elapsed from time of prior platinum treatment. Patients were required to have a performance status of < or =2 and normal hepatic and renal function. Response to therapy and toxicity was assessed using standard criteria. Chi-square and Student's t tests were used as appropriate. Survival was assessed with Kaplan-Meier method. RESULTS: All 40 patients enrolled were assessable for response. The mean age of the patients was 63.2 years (range 43-85). Median time to progression from initial treatment was 11.8 months. A total of 286 cycles of chemotherapy were administered with an average of 7.1 cycles per patient. Overall median time to progression (TTP) with 3-day topotecan treatment was 21 weeks (range 6-43 weeks). Of the 33 patients with measurable disease, 24% (11-42%, 95% CI) demonstrated a response. Seven patients had CA-125 evaluable disease with a response of 43% (10-89%, 95% CI). Median progression-free survival (PFS) was 16 weeks (range 12-21 weeks, 95% CI). Median overall survival was 106 weeks (range 76-117 weeks, 95% CI). Assessment of toxicity by patient showed 90% demonstrating grade 3/4 neutropenia with the vast majority being uncomplicated. No severe non-hematological toxicity was observed. CONCLUSION: Administration of topotecan as a 3-day regimen is feasible with demonstrable activity and tolerable toxicity. Critical comparison to the 5-day regimen in a randomized fashion is warranted.     

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy

OBJECTIVE: To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. METHODS: Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 > or = 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m(2)) was given on day 1, and 5-Fluorouracil (370 mg/m(2)) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. RESULTS: Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. CONCLUSION: Oxaliplatin and 5-Fluorouracil/Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer.     

Advanced stage mucinous epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience

OBJECTIVE: Mucinous epithelial ovarian cancer (mEOC) representing about 10% of all EOC are known to be possibly resistant to platinum-based chemotherapy and bear a poorer prognosis with respect to other subtypes of EOC. This study was undertaken to compare response and survival to platinum-based chemotherapy between patients with advanced stages III and IV mEOC and serous EOC (sEOC). METHODS: A retrospective analysis was performed in 47 patients with advanced stage of mEOC treated with first-line platinum-based chemotherapy in the context of several study protocols of the Hellenic Cooperative Oncology Group (HeCOG) between 6/7/1983 and 25/2/2003. The outcome was compared to that of 94 patients with sEOC treated with the same protocols during the same study period (ratio mucinous: serous 1:2). RESULTS: One hundred forty-one patients (47 stages III and IV mEOC, 94 stages III and IV sEOC) treated with platinum-based chemotherapy were analyzed. The overall response rate for mEOC was 38.5% (complete remission 18%) (95% CI 23.4-55.4%) and 70% (complete remission 47%) (95% CI 58.5-80.3%) for sEOC (P = 0.001). After a median follow-up of 77.8 months, median survival and time to tumor progression (TTP) were not significantly different between the two groups (33.2 months [95% CI 23.3-43.1 months] vs. 38.0 months [95% CI 26.8-49.2 months], P = 0.46, 11.8 months [95% CI 7.2-16.4 months] vs. 20.0 months [95% CI 15.7-24.2 months], P = 0.18, respectively). CONCLUSION: Patients with mEOC have significantly lower response to first-line platinum-based chemotherapy compared to patients with sEOC. This low response to platinum-based chemotherapy was not translated in inferior TTP or survival. Our data indicate that a new strategy for chemotherapy in mEOC should be adopted, one that focuses on new agents without cross-resistance to platinum agents.     

Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum

OBJECTIVE: Previously reported data have suggested the lack of complete cross-resistance between docetaxel and paclitaxel in ovarian cancer. We wished to evaluate the biological and clinical activity of docetaxel in a patient population with well-characterized platinum and paclitaxel-refractory ovarian cancer. METHODS: In this single-institution phase 2 trial, 30 women with advanced ovarian cancer whose disease had either failed to respond to primary platinum-paclitaxel chemotherapy or where the cancer had progressed within 3 months of their last treatment with both a platinum agent and paclitaxel were treated with single agent docetaxel (75 mg/m(2) q 3 weeks). Due to a prior history of excessive chemotherapy-induced neutropenia, 3 patients initiated treatment at a dose of 60 mg/m(2). RESULTS: The median number of courses of docetaxel delivered on this protocol was 3 (range 1-7), with 7 patients requiring dose reductions due to treatment-related side effects. The most common toxicities included grade 4 neutropenia, neutropenic fever, and grade >/=2 fatigue experienced by 9 (30%), 2 (7%), 5 (17%) patients, respectively. Three patients (10%) achieved both an objective response (by CA-125 criteria) and symptomatic improvement (e.g., decrease in pain and ascites). The durations of responses were 3, 4, and 6 months. CONCLUSION: Single-agent docetaxel has modest, but definite activity in patients with well-characterized platinum and paclitaxel-resistant ovarian cancer. Use of this drug should be considered a rational management approach in appropriately selected patients in this clinical setting.     

以吉西他滨为基础的联合化疗治疗复发性铂类耐药卵巢上皮性癌的临床观察

目的 评价以吉西他滨为基础联合异环磷酰胺和蒽环类药物治疗复发性铂类耐药卵巢上皮性癌(卵巢癌)的近期疗效及毒副反应.方法 对60例复发性铂类耐药卵巢癌患者应用吉西他滨、异环磷酰胺和蒽环类药物联合化疗方案[吉西他滨800 mg/m2,第1、8天;异环磷酰胺1.5 g/m2,第1～3天;多柔比星(其他名称:阿霉素)40 mg/m2或表柔比星(其他名称:表阿霉素)60 mg/m2(第1天),或米托蒽醌10 mg/m2(第1、8天);21～28 d重复],回顾性分析其临床病理资料.结果 60例患者共接受172个疗程的化疗.完全缓解0例,部分缓解22例(37%,22/60),稳定23例(38%,23/60),疾病进展15例(25%,15/60),临床总获益率75%(45/60);中位无疾病进展生存期为7个月,中位总生存期为20个月.主要不良反应为骨髓抑制,白细胞减少发生率达82%(49/60),其中Ⅲ～Ⅳ度占31%(15/49);消化道反应均为Ⅰ、Ⅱ度,占42%(25/60).结论 以吉西他滨为基础的联合化疗可作为铂类耐药的复发性卵巢癌的治疗方案之一,毒副反应可以耐受.     

Brain metastases as isolated site of relapse in patients with epithelial ovarian cancer previously treated with platinum and paclitaxel-based chemotherapy

Brain metastases in patients with epithelial ovarian cancer (EOC) have an estimated incidence of 0.3-1.9% and are isolated in up to 50% of these patients. The risk factors and the prognostic significance of isolated central nervous system (CNS) relapse in patients with EOC who received primary treatment with platinum and paclitaxel have not been identified. We conducted a retrospective study in patients with EOC who relapsed with isolated brain metastases and report our experience. Two hundred sixty-seven patients with stages III and IV EOC, in clinical complete remission after first-line treatment with platinum and paclitaxel, were included in our analysis. After a median follow-up of 65 months, 150 patients had relapsed. Eight patients (5%) had isolated brain metastases. Patient and disease characteristics did not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS. Median time to first disease relapse, overall survival, and survival after relapse did not differ significantly between patients with brain metastases and those with relapse outside the CNS. Two patients have died 6 and 12 months after the diagnosis of brain metastases, and 5 patients are alive 4-35 months after the diagnosis of isolated brain metastases. Three patients remain free of disease 4-18 months after treatment with radiotherapy and systemic chemotherapy for their CNS metastatic disease. Patients with isolated brain metastases have comparable survival to patients with relapse outside the CNS, and long-term remission can be achieved in some cases, provided that systemic chemotherapy is added to local treatment.     

Biweekly gemcitabine and cisplatin in platinum-resistant/refractory, paclitaxel-pretreated, ovarian and peritoneal carcinoma

OBJECTIVES: Synergism between gemcitabine and cisplatin is supported by preclinical and clinical data. The present study explores the efficacy of a biweekly regimen in platinum-resistant/refractory, paclitaxel-pretreated ovarian and peritoneal cancer. METHODS: 50 paclitaxel-pretreated patients with platinum-resistant/refractory ovarian or peritoneal carcinoma who had previously received paclitaxel chemotherapy, were treated with six cycles of gemcitabine 1000 mg/m(2) followed by cisplatin 40 mg/m(2) on days 1 and 15, repeated every 4 weeks. RESULTS: The median platinum-free interval (PFI) was 4 months while the median number of previous treatment lines was 2. Chemotherapy was well tolerated. Objective responses were observed in 31.5% of evaluable patients (n=35). CA125 response was observed in 68% of patients with elevated CA125 (n=41). Median overall survival (OS) was 13.2 months (95% Confidence Interval, CI: 10.2-16.2) while progression-free survival (PFS) was 4.9 months (95%CI: 3.5-6.4). A PFI of less than 3 months was associated with lower objective response rates (15.8% versus 50%, p=0.03). CONCLUSIONS: Biweekly gemcitabine and cisplatin is feasible for patients with platinum-resistant ovarian or peritoneal cancer and is associated with a favorable toxicity profile. In a population with recent exposure to platinum, a PFI of less than 3 months was the major factor influencing response to chemotherapy.     

拓扑替康联合铂类治疗晚期卵巢癌的疗效观察

目的:评价拓扑替康联合铂类(TPT+铂类)治疗晚期卵巢癌的疗效及安全性。方法:回顾分析2000年4月至2004年12月收治的符合入选标准的晚期卵巢上皮性癌患者45例,其中初治20例,复治25例。比较初治患者与同期收治的接受紫杉醇加铂类(TP方案)及环磷酰胺加铂类(PC方案)治疗者的临床有效率、中位无进展生存时间和中位生存时间。复治患者则比较一线经铂类或经紫杉醇治疗复发者的有效率、中位无进展生存时间和中位生存时间。结果:初治患者中,TPT+铂类组有效率为75.0%,中位无进展生存时间及中位生存时间分别为17.8月及29.7月,而TP组分别为82.5%,20.9月,35.3月,PC组分别71.4%,14.6月,27.8月,TPT加铂类组与TP组、PC组相比,差异无显著性(P>0.05)。复治患者中,总有效率为28.0%,一线经铂类或经紫杉醇治疗复发患者的有效率为33.3%、23.1%,中位无进展生存时间分别为11.3月、8.4月,中位生存时间分别为18.3月,17.3月,差异无显著性(P>0.05)。非血液性毒性轻微。结论:TPT联合铂类治疗晚期卵巢癌疗效肯定,特别是对复发病例有较好疗效,耐受性良好。