紫杉醇与奥沙利铂联合化疗治疗晚期卵巢上皮性癌的临床观察

目的:观察紫杉醇与奥沙利铂联合化疗对晚期卵巢上皮性癌近期疗效及毒副反应.方法:晚期卵巢上皮性癌40例,采用紫杉醇与奥沙利铂联合化疗方案(紫杉醇135 mg/m2,奥沙利铂150 mg/m2)全身化疗,3周为1疗程,至少完成4个疗程观察疗效.结果:Ⅲ期有效率为70.0%;IV期有效率为50.0%.白细胞下降发生率70.0%(28/40),但62.5%(25/40)均为Ⅰ～Ⅱ级;胃肠道反应发生率57.5%(23/40);所有患者均未因毒副反应中断或退出治疗.结论:紫杉醇与奥沙利铂联合化疗效果较好,毒副反应较轻.     

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.     

脂质体多柔比星联合卡铂治疗复发性卵巢上皮性癌的临床研究

目的 评价脂质体多柔比星+卡铂方案治疗复发性卵巢上皮性癌(卵巢癌)的疗效和副反应.方法 2003年7月-2007年12月间北京肿瘤医院妇瘤科共收治67例卵巢癌(包括原发性腹膜腺癌8例,因其生物学行为和治疗同卵巢癌,故列入本研究)患者,所有患者初次治疗均接受了肿瘤细胞减灭术及以铂类为基础的联合化疗,复发后使用脂质体多柔比星(35～40 ms/m2)+卡铂(血浆浓度时间曲线下面积=5,每4周为1个疗程)作为一线或二线及以上化疗方案治疗,观察其有效率和生存率,并且评估其化疗副反应的发生率.结果 67例患者中,49例患者可进行疗效评估,其中完全缓解23例(47%),部分缓解13例(27%),病情平稳3例(6%),疾病进展10例(20%),有效(完全缓解+部分缓解)率为73%;中位疾病无进展生存时间为8个月;1年和2年生存率分别为73%和55%.67例患者中,2例因过敏样输液反应终止治疗;4例出现胸闷为主要症状的急性输液反应(因停药后再次使用时无任何不良反应发生,所以未终止治疗);2级和3级手足综合征分别为2例(3%)和3例(4%);2例(3%)患者出现4级121腔炎;3级白细胞减少8例(12%).无一例发生4级白细胞减少或与药物相关的心脏毒性反应.结论 脂质体多柔比星+卡铂方案治疗复发性卵巢癌具有一定的疗效,患者对治疗的耐受性良好,可作为治疗复发性卵巢癌的选择之一.     

复发性卵巢上皮性癌再次应用铂类药物的近期疗效及其相关因素分析

目的　探讨复发性卵巢上皮性癌 (卵巢癌 )再次应用铂类药物进行化学药物治疗 (化疗 )的近期疗效及其相关因素。方法　 1998年 1月～ 2 0 0 2年 10月收治对铂类药物敏感的卵巢癌患者 4 1例 ,回顾性分析 4 1例复发后再次应用铂类药物化疗的近期疗效 ,并选择年龄、初次手术结果、化疗疗程数、化疗是否规范、血清CA12 5水平、是否随访、复发间隔时间、复发部位及复发病灶数等 37个因素进行疗效分析。结果　再次应用铂类药物的近期有效率为 5 6 % ,无严重毒副反应 ;疗效与复发后化疗是否规范有显著相关性 (r=0 92 ,P <0 0 5 ) ,其中规范化疗的近期有效率为 76 % (19/ 2 5 ) ,不规范化疗为 2 5 % (4/ 16 )。近期有效率与其他因素无显著相关性 (P >0 0 5 )。结论　对铂类药物敏感的复发性卵巢癌患者可再次应用铂类药物化疗 ,其近期疗效与复发后是否规范化疗有关。     

紫杉醇联合铂类治疗持续耐药及复发性妊娠滋养细胞肿瘤的疗效分析

目的:评价紫杉醇联合铂类药物化疗方案治疗持续耐药及复发性妊娠滋养细胞肿瘤(GTN)患者的疗效及安全性。方法:回顾性分析2006年1月至2013年1月,在北京协和医院接受紫杉醇联合铂类化疗方案治疗的25例持续耐药及复发性GTN患者的治疗情况及最终治疗结局。结果:25例持续耐药及复发性GTN患者共接受了115疗程的紫杉醇联合铂类的化疗方案,平均每例4.6±2.2(2~10)疗程,具体包括紫杉醇+顺铂(TP)方案52疗程、紫杉醇+卡铂(TC)方案56疗程及紫杉醇+依托泊苷/紫杉醇+顺铂(TE/TP)方案7疗程。在停止化疗时,血清学完全缓解14例,部分缓解4例,治疗无效7例,完全缓解率为56.0%(14/25),总缓解率为72.0%(18/25),血清学完全缓解后的复发率为35.7%(5/14),平均复发时间为95.4±18.4天(约3.2个月)。紫杉醇联合铂类方案的毒副反应主要为骨髓抑制、消化道反应、肝肾损伤及过敏等,发生Ⅲ~Ⅳ度骨髓抑制患者比例为48.0%,未发生致死性副反应。结论:紫杉醇联合铂类对持续耐药及复发性GTN患者是可供选择的化疗方案。     

手术及术后化疗治疗有复发中危和高危因素的ⅠB～ⅡA期宫颈癌68例疗效分析

目的:探讨宫颈癌根治术和盆腔淋巴结切除术及术后单纯化疗在有复发中危和高危因素的ⅠB～ⅡA期宫颈癌患者治疗中的效果。方法:选取在北京大学第一医院治疗的68例ⅠB～ⅡA期宫颈癌患者,初始治疗为宫颈癌根治术和盆腔淋巴结切除术,根据术后病理检查结果分为复发中危因素组(中危组)37例(侵犯宫颈深度>1/2宫颈厚度、低分化、肿瘤直径≥4cm、淋巴血管间隙受累)和复发高危因素组(高危组)31例(淋巴结转移、宫旁肿瘤侵犯、切缘阳性)。对所有患者术后辅助单纯化疗,中危组3～4个疗程,高危组4～6个疗程。宫颈鳞癌及腺鳞癌化疗为BIP方案(博来霉素+异环磷酰胺+顺铂/卡铂),腺癌化疗为TP方案(紫杉醇+顺铂/卡铂)。总结患者的3年累积无瘤生存率、复发率和手术及化疗的并发症及毒副反应。结果:37例中危组患者3年累积无瘤生存率为93.1%,31例高危组患者3年累积无瘤生存率为85.4%,两组比较,差异无统计学意义(P>0.05)。68例患者的总复发率为10.3%(7/68),中危组复发率为8.1%,高危组复发率为12.9%。中危组和高危组盆腔局部复发率分别为5.4%和6.5%。两组各项化疗毒副反应发生率比较,差异无统计学意义(P>0.05)。结论:宫颈癌手术及术后化疗对于有复发中危和高危因素的ⅠB～ⅡA期患者是一种可行的治疗选择,患者可耐受手术联合单纯化疗的并发症和毒副反应,并获得较好的近远期疗效。     

超大剂量顺铂治疗卵巢上皮性癌初步报道

目的研究超大剂量顺铂治疗晚期卵巢癌的临床疗效和可行性.方法对23例FGO期别≥Ic的晚期卵巢癌施行超大剂量顺铂(120～150mg/m2)化疗,采用David法计算顺铂的剂量强度、UICC和WHO标准评定临床疗效和毒副反应.结果共进行100疗程化疗,顺铂剂量强度(DI)3.08±0.92,总剂量强度(TD)12.08±3.92,临床完全反应率60.86%,有效率65.22%,顺铂DI、TDI和近期疗效无关(P＞0.05).23例中无一例因化疗毒副反应死亡,但出现剂量限制毒性21疗程.初治病例中位生存14个月,无瘤中位生存13个月.结论超大剂量顺铂治疗晚期卵巢癌难以达到计划顺铂剂量强度,在人体内提高顺铂剂量并不一定改善化疗疗效.     

影响复发上皮性卵巢癌化疗疗效的临床病理因素分析

目的:分析影响铂类敏感型及耐药型复发上皮性卵巢癌(EOC)患者预后的相关临床病理因素。方法:回顾分析1985年1月至2011年11月广西医科大学附属肿瘤医院收治的复发EOC患者83例,其中铂类敏感型56例,耐药型27例。采用Kaplan-meier生存率曲线、Log-rank test检验和Cox模型多因素回归分析法分析影响复发EOC患者预后的相关因素。结果:(1)铂类敏感型复发EOC患者的中位无进展生存期(PFS)为11个月(95%CI 9.105～12.895),中位总生存期(OS)为16个月(95%CI 13.144～18.856);铂类耐药型复发EOC患者的中位PFS为8个月(95%CI 4.219～11.781),中位OS为10个月(95%CI 3.824～16.176)。(2)复发后伴有腹水、复发后化疗方案、化疗疗程、化疗效果是影响敏感型复发EOC患者的重要预后因素(P<0.05);无复发生存时间(RFS)、复发后伴有腹水、复发部位、化疗效果是影响耐药型复发EOC患者的重要预后因素(P<0.05)。(3)复发后化疗疗程数、复发后伴有腹水、化疗疗效是影响敏感型复发EOC患者预后的独立危险因素,而复发部位是影响耐药型复发EOC患者预后的独立危险因素。结论:铂类敏感型患者复发后宜选择与一线类似的铂类联合方案化疗,并尽可能化疗至6疗程。复发病灶位于盆腹腔是影响耐药型患者预后的独立危险因素,应积极治疗。     

复发卵巢癌的理想序贯治疗

复发卵巢癌姑息治疗的目的是控制疾病相关症状、降低治疗的副反应,延长生存期,延迟病情进展的时间,维持或更好地提高生存质量。 复发卵巢癌首次铂类化疗的无治疗间期长短明显影响患者再接受铂类化疗的缓解率。铂类难治性卵巢癌(6个月内复发)再接受铂类治疗的缓解率约10％而铂类敏感者(6个月后复发)达28％。复发卵巢癌常使用铂类、紫杉醇联合化疗,但此方案对无治疗问期短者,缓解率低。无铂类问期与二线铂类联合联合化疗的缓解率有关:6～12个月者再化疗缓解率为25％～30％。2年者再化疗缓解率升至60％～70％。卡铂、     

Surgical Treatment Combined with Postoperative Adjuvant Chemotherapy Offer a Viable Option to the Cervical Cancer in Stage ⅠB ～ⅡA with Moderate and High-Risk Factor for Recurrence

目的:探讨宫颈癌根治术和盆腔淋巴结切除术及术后单纯化疗在有复发中危和高危因素的ⅠB～ⅡA期宫颈癌患者治疗中的效果.方法:选取在北京大学第一医院治疗的68例ⅠB～ⅡA期宫颈癌患者,初始治疗为宫颈癌根治术和盆腔淋巴结切除术,根据术后病理检查结果分为复发中危因素组(中危组)37例(侵犯宫颈深度＞ 1/2宫颈厚度、低分化、肿瘤直径≥4 cm、淋巴血管间隙受累)和复发高危因素组(高危组)31例(淋巴结转移、宫旁肿瘤侵犯、切缘阳性).对所有患者术后辅助单纯化疗,中危组3～4个疗程,高危组4～6个疗程.宫颈鳞癌及腺鳞癌化疗为BIP方案(博来霉素+异环磷酰胺+顺铂/卡铂),腺癌化疗为TP方案(紫杉醇+顺铂/卡铂).总结患者的3年累积无瘤生存率、复发率和手术及化疗的并发症及毒副反应.结果:37例中危组患者3年累积无瘤生存率为93.1％,31例高危组患者3年累积无瘤生存率为85.4％,两组比较,差异无统计学意义(P＞0.05).68例患者的总复发率为10.3％ (7/68),中危组复发率为8.1％,高危组复发率为12.9％.中危组和高危组盆腔局部复发率分别为5.4％和6.5％.两组各项化疗毒副反应发生率比较,差异无统计学意义(P＞0.05).结论:宫颈癌手术及术后化疗对于有复发中危和高危因素的ⅠB～ⅡA期患者是一种可行的治疗选择,患者可耐受手术联合单纯化疗的并发症和毒副反应,并获得较好的近远期疗效.     

Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37-78), were enrolled. A median of six cycles (range, 1-8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6-9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9-21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.     

Combined Chemotherapy Using Cisplatin, Ifosfamide and Bleomycin (PIB) in the Treatment of Advanced and Recurrent Cervical Carcinoma

Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial.     

Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study

OBJECTIVE: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluoruracil (5-FU) and high-dose leucovorin (LV) (FOLFOX-4) in patients with platinum-resistant, taxane-pretreated recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients, with a median age of 58 years (range 33-77), were treated with oxaliplatin 85 mg m(-2) as a 2-h infusion on day 1, LV 200 mg m(-2) day(-1) as a 2-h infusion followed by bolus 5-FU 400 mg m(-2) day(-1) and a 22-h infusion of 5-FU 600 mg m(-2) day(-1) for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. RESULTS: The vast majority of patients had performance status 0 or 1 and 76.3% had > or = 2 metastatic sites. A median number of four cycles per patient (range, 1-8) were administered. Based on an intention-to-treat analysis, 3 patients (7.9%) achieved a complete response (CR) and 8 (21.1%) achieved a partial response (PR), for an overall response rate of 29%. Another 29% of patients had stable disease (SD). The median relapse-free survival was 5.2 months (range 2.5-17), the median time to tumor progression was 4.8 months (range 0.6-19), and the median overall survival was 10.1 months (range 0.2-36). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 29% and 21.1% of patients, respectively. Febrile neutropenia was encountered in 3 patients (7.9%), who were successfully treated. Grade 3/4 neurotoxicity developed in 15.8% of patients; neurotoxicity gradually declined after treatment discontinuation. Alopecia, nausea-vomiting, diarrhea, mucositis, and asthenia were not a serious problem. There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin and 5-FU/LV (FOLFOX-4) appears to be an effective regimen with a good toxicity profile for the treatment of platinum-resistant, taxane-pretreated ovarian cancer.     

Ifosfamide and vinorelbine in advanced platinum-resistant ovarian cancer: excessive toxicity with a potentially active regimen

OBJECTIVES: The aim of this study was to determine the activity and toxicity of a vinorelbine and ifosfamide combination in platinum-resistant advanced ovarian cancer. PATIENTS AND METHODS: Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x 3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1 and 8. Treatment was repeated on a 21-day schedule. In order to avoid unacceptable toxicity in this subset of patients where the chemotherapy is mainly palliative, the Bryant and Day two-stage phase II trial design incorporating toxicity considerations was chosen. A cutoff point for the response rate (10%) and for severe toxicity (25%) was established for the first 14 patients. RESULTS: Between February 1997 and December 1998, 11 paclitaxel and platinum-resistant patients and 1 potentially platinum-sensitive patient were treated. Five patients (41%) experienced grade 3-4 central nervous toxicity requiring hospital admission. In accordance with the Bryant and Day design, the study was stopped early because greater than 25% of the first 14 patients developed grade 3-4 neurotoxicity. A retrospective review of clinical characteristics of these patients showed at least one well-known risk factor associated with ifosfamide central toxicity. Hematological toxicity was common, mainly grade 4 neutropenia, which was observed in all but 1 patient, usually of short duration, and there were 4 episodes of neutropenic fever. Ten patients were evaluated for response. Two complete responses and 1 partial response according to CA-125 criteria were observed. CONCLUSION: This combination may be active in platinum-resistant ovarian cancer but the high toxicity encountered, principally neurotoxicity in those with large central pelvic masses, means that further studies with this schedule may not be warranted.     

A multicenter phase II study of pegylated liposomal doxorubicin and oxaliplatin in recurrent ovarian cancer

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) and oxaliplatin (LOHP) are active as single agents in the treatment of recurrent ovarian cancer (ROC). This phase II study investigated the safety and activity of PLD and LOHP used in combination to treat ROC. METHODS: Eligibility criteria included disease recurrence after one (45%) or more lines (55%) of chemotherapy, performance status 3 months. Treatment was 40 mg/m(2) PLD and 120 mg/m(2) LOHP, administered over 2 days, every 3 weeks. Response to therapy was assessed using the RECIST criteria. RESULTS: Forty patients with ROC enrolled in the study from 10/2001 to 10/2005; 27 patients were platinum-sensitive and 13 were platinum-resistant. Major toxicities included grade 3-4 neutropenia (37%) and grade 2 palmar-plantar erythrodysesthesia (10%). The overall response rate was 67.5%, with 30% stable disease rate and 2.5% progressive disease rate. The median progression-free survival (PFS) was 9.6 months, while median overall survival was 18.3 months, with no statistically significant difference in PFS between platinum-resistant and platinum-sensitive patients. CONCLUSION: We conclude that the combination of PLD and LOHP shows activity in ROC with a manageable toxicity profile and can be safely administered in heavily pre-treated patients.     

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。     

Treatment of gynecological adenocarcinomas with a combination of ifosfamide, adriamycin and cisplatin

Fourteen evaluable patients with gynecologic adenocarcinoma (7 ovarian, 4 endometrial, 2 peritoneal and one breast cancer) were treated with ifosfamide (1 g/m2 X 5 days), adriamycin (50 mg/m2) and cisplatin (50 mg/m2) combined chemotherapy (IAP). All the patients had measurable disease, and three were refractory cases who had received prior chemotherapy including two CAP (cyclophosphamide, adriamycin and cisplatin). To avoid hemorrhagic cystitis induced by ifosfamide, uroprotective mesna (400 mg/body X 3) was used following ifosfamide infusion. The 5-day schedule of IAP treatment brought a 100% response rate in these patients. Complete responses were observed in 3 patients and lasted 6, 10 and 12 months. Partial responses were achieved in 11 patients including two with CAP refractory ovarian cancer, although the remission in previously treated patients was of short duration. Hematologic side effects of the IAP regimen were severe, showing grade 4 leucopenia in 85.7% of the patients, and it required maximal anti-infection treatments. Mesna resulted in microhematuria in only one patient. Despite high age of the patients (mean age: 60.1 years) in this study, CNS (central nervous system) toxicities associated with ifosfamide and mesna treatment were minimal. The results suggested that the IAP combination therapy was effective and acceptable in the control of gynecological adenocarcinomas.     

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.     

Phase II evaluation of 3-day topotecan with cyclophosphamide in the treatment of recurrent ovarian cancer

OBJECTIVE: The aim of this trial was to investigate the toxicity and efficacy of a 3-day topotecan administration schedule in combination with cyclophosphamide in the management of recurrent ovarian cancer. METHODS: Patients with recurrent measurable ovarian cancer who had up to two prior chemotherapy regimens for the management of their disease participating in this phase II trial were to receive topotecan at a dose of 1.25 mg/m(2)/day x 3 days in combination with cyclophosphamide at 600 mg/m(2) on Day 1 every 21 days. Dose escalation and reductions were permitted. RESULTS: A total of 36 patients (median age = 65; range 37-84) were treated with this combination regimen. Seventeen were platinum-sensitive and 19 were platinum-resistant. A total of 169 cycles of chemotherapy was administered (median = 4; range 1-10). Major toxicity included grade 4 neutropenia (68.6%), neutropenic fever (7.1%), grade 3 thrombocytopenia (18.3%), and requirement for blood transfusion (19.5%). Dose escalation was possible in 3 (8.3%), and dose reduction was required in 14 (38.9%) patients. Overall response rate was 25 and 44.5% stable disease. Median progression-free interval and overall survival was 5.4 and 23.5 months, respectively, independent of platinum sensitivity. CONCLUSION: The 3-day topotecan schedule in combination with cyclophosphamide appears to have good activity in recurrent ovarian cancer regardless of platinum sensitivity. Neutropenia was the only severe toxicity and was less prevalent than other reported trials of topotecan. This tolerable regimen offers patients more convenience and appears to have moderate activity.