Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.     

经腹腔和静脉双途径应用紫杉醇化疗治疗晚期卵巢癌

目的：观察并评价紫杉醇(泰素)加顺铂经腹腔和静脉化疗治疗晚期卵巢癌的近期疗效及其毒副反应。方法：8例Ⅲ或Ⅳ期卵巢癌患接受泰素40mg／m^2 顺铂20～40mg／m^2腹腔注入，泰素40mg／m^2静脉滴注，每周1次，连用3周为一疗程，2个疗程后进行评价。结果：全组8例患中获得PR4例，总有效率50％；控制腹水的有效率达100％。结论：泰素和顺铂经腹腔和静脉化疗治疗晚期卵巢癌疗效肯定，毒副反应轻，值得临床进一步研究和应用。     

中晚期卵巢癌术后顺铂腹腔联合紫杉醇静脉化疗的临床观察

目的:观察顺铂腹腔联合紫杉醇静脉化疗治疗中晚期卵巢癌术后患者的临床疗效和安全性.方法:回顾性分析我院2006-01-2009-12行细胞减灭术Ⅱ～Ⅳ期卵巢癌76例患者,顺铂腹腔联合紫杉醇静脉化疗36例为治疗组,并以同期行顺铂联合紫杉醇静脉化疗患者40例作为对照.比较两组患者无进展生存期(PFS)、生存率和不良反应.结果:治疗组PFS 27个月,对照组PFS 23个月,P＜0.05.治疗组1、2和3年生存率分别为97.22％(35/36)、94.44％(34/36)和88.88％(32/36),对照组1、2和3年生存率分别为95.00％(38/40)、90.00％(36/40)和77.50％(31/40).治化疗组呕吐及肾功能损伤低于对照组,而腹痛高于对照组.结论:顺铂腹腔联合紫杉醇静脉化疗治疗中晚期卵巢癌术后患者可延长患者PFS及生存率,毒副反应轻,值得临床应用.     

First-line chemotherapy with intraperitoneal cisplatin and intravenous cyclophosphamide in ovarian carcinoma. A preliminary report

Between August 1982 and October 1986, the feasibility and activity of five cycles of intraperitoneal (i.p.) cisplatin (CDDP) (90 mg/m2 in 6 h dwelling) and i.v. cyclophosphamide (600 mg/m2) were studied in 24 previously untreated patients with ovarian carcinoma having small or no residual disease after cytoreductive surgery. Six patients (25%) had local complications requiring catheter removal before the end of therapy. Fifteen of the 21 patients (71%) evaluable for activity achieved or maintained a pathologic complete remission. The median disease-free survival was 29+ months (range 18-58+ months). Three patients with tumor progression (two patients previously without evidence of disease, and one patient with minimal residual disease), and three partial responders were documented by laparotomy at the end of therapy. Two patients who achieved pathologic complete response relapsed at 20 and 36 months. All treatment failures (eight cases, 38%) occurred in the peritoneal cavity. Since patients were selected for having the most favorable tumor characteristics to benefit from i.p. treatment, our findings may cast some doubt on the actual contribution of i.p. CDDP at a dose of 90 mg/m2 in the treatment of patients with ovarian carcinoma and small residual disease in the peritoneal cavity.     

以大剂量顺铂为主腹腔内化疗治疗晚期卵巢癌临床观察

目的　评价大剂量顺铂和常规剂量顺铂腹腔化疗对晚期卵巢癌的疗效。方法　将 1994年至1998年在我院住院治疗的晚期卵巢癌患者 5 3例随机分为大剂量顺铂组 2 8例 ,常规剂量顺铂组 2 5例。每周腹腔化疗一次 ,3～ 6周为一疗程。结果　大剂量顺铂组和常规剂量顺铂组其有效率和中位生存期分别为 89 2 9%、6 4 0 0 %和 13月、8 5月 (P <0 .0 5 )。如果腹腔内化疗加全身化疗 ,则疗效优于单纯腹腔化疗组。结论　大剂量顺铂腹腔化疗治疗晚期卵巢癌其疗效明显优于常规剂量顺铂组。     

Doxorubicin and cyclophosphamide, alternated with bleomycin and mitomycin C as a second-line regimen in advanced ovarian carcinoma resistant to cisplatin-based chemotherapy.

Fourteen patients with advanced ovarian carcinoma (FIGO stages III-IV) resistant to cisplatin were submitted to an alternating regimen with doxorubicin (A), cyclophosphamide (C), bleomycin (B) and mitomycin C (M). All patients had measurable disease on entry into the study. No responses were observed while 3 patients, previously showing no change in cisplatin, had disease stabilization lasting 3, 4 and 6 months, respectively. All but 1 patient died with a median survival from the start of ACBM therapy of 7 months (range 6-11). ACBM-induced toxicity was remarkable with 50% grade II-III myelotoxicity which required a dose reduction in 43%, treatment delays in 64% and treatment discontinuation in 14%. All patients suffered from mild to moderate nausea and vomiting while reversible alopecia was seen in 42.8%. The lack of response and the substantial toxicity observed suggest that the ACBM regimen in the doses and schedule employed is not beneficial in ovarian carcinoma resistant to cisplatin.     

Survival with intraperitoneal cisplatin in advanced ovarian cancer after second-look laparotomy.

We studied survival in 36 patients with Stage III/IV ovarian cancer who received intraperitoneal high-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g), after intravenous (i.v.) cisplatin-based chemotherapy followed by second-look laparotomy. Complete responders were scheduled for three courses of IP chemotherapy, and others for six. Eight patients (22%) did not complete treatment (6 catheter failures and 2 renal failures). Peritoneal cytology remained positive in 6 patients (17%). Median overall and progression-free survival after second-look laparotomy were 44 and 37 months, respectively, for 13 complete responders to i.v. chemotherapy; 24 months and 11 months for patients with residual tumors less than 2 cm (17 cases); 15 and 12 months with tumors greater than 2 cm (6 cases). There was a significant difference in overall (p = 0.05) and progression-free (p = 0.001) survival between complete responders to i.v. chemotherapy and patients whose tumor was less than 2 cm. We find no evidence that high-dose cisplatin-based intraperitoneal chemotherapy given after second-look laparotomy will enhance survival in advanced ovarian cancer with zero or minimal residual disease.     

Intraoperative intraperitoneal chemotherapy with cisplatin in epithelial ovarian cancer

Objective

To assess retrospectively the feasibility of intraoperative intraperitoneal (IP) chemotherapy with cisplatin in epithelial ovarian cancer.

Methods

IP chemotherapy during optimal staging surgery was performed in 10 patients who were diagnosed with primary epithelial ovarian cancers between April 2008 and February 2011. Cisplatin (70 mg/m² in 1 L normal saline solution) was administered in the abdominal cavity for 24 hours postoperatively and then adjuvant chemotherapy was started 2-4 weeks after surgery. Perioperative toxicity of the combined treatment was evaluated until the initiation of postoperative adjuvant chemotherapy.

Results

A total of 23 adverse events were observed in 9 of 10 patients (grade 1, 7; grade 2, 13; grade 3, 3; grade 4, 0). In descending order of frequency, adverse events affected the gastrointestinal system (n=14), hematologic system (n=6), pulmonary system (n=2), and genito-urinary system (n=1). The adverse events did not affect adjuvant systemic chemotherapy schedules. One patient experienced disease recurrence in the liver 16 months after surgery. The remaining 9 patients have been well controlled by chemotherapy and/or observation during the follow-up period of 4 to 39 months after surgery.

Conclusion

Intraoperative IP chemotherapy with cisplatin during surgical procedures is considered feasible for the treatment of primary epithelial ovarian cancer. Further studies, including long-term, prospective and comparative trials, are needed to validate the efficacy of this combined therapy.     

顺铂腹腔灌注联合多西他赛静脉化疗方案在晚期卵巢癌患者中的应用效果比较

目的 探讨顺铂腹腔灌注联合多西他赛静脉化疗对卵巢癌晚期患者的治疗效果和不良反应.方法 选取卵巢癌晚期患者98例作为研究对象,采用随机数字表法分为观察组和对照组各49例.观察组采用多西他赛静脉输注联合顺铂腹腔灌注治疗,对照组采用多西他赛和顺铂静脉滴注化疗,两组剂量相同,且均化疗6个周期.结果 两组不良反应主要分为静脉化疗骨髓抑制和肝损伤,两组患者静脉化疗骨髓抑制发生情况比较,差异有统计学意义(P＜0.05);两组患者部分缓解率比较,差异有统计学意义(P＜0.05);观察组的临床有效率和临床受益率均高于对照组,差异有统计学意义(P＜0.05).结论 采用顺铂腹腔灌注联合多西他赛静脉化疗的方式对晚期卵巢癌的患者进行化疗能够提高疗效,减轻患者痛苦.     

晚期胃癌静脉合并腹腔化疗近期疗效观察

目的：观察并评价静脉合并腹腔化疗治疗晚期胃癌的近期疗效及毒副反应。方法：用ELF方案（CF、5－Fu、VP16）静脉滴注加DDP腹腔化疗61例晚期胃癌病人，观察并记录近期疗效和毒副反应。结果：全组患者总有效率为57.4%，其中CR率为9.8%，毒副反应较轻，主要为白细胞下降发生率为95.1%，血小板下降发生率为27.8%。结论：静脉加腹腔化疗治疗晚期胃癌疗效肯定，毒副反应轻，值得临床研究应用。     

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study

Objective

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC.

Methods

This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease.

Results

Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months.

Conclusion

CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.     

Consolidation with intraperitoneal cisplatin in first-line therapy of advanced ovarian cancer

Seventy-five patients with advanced epithelial ovarian cancer were treated with a combined modality regimen of systemic, induction chemotherapy followed by intraperitoneal therapy (IPT). All patients underwent initial surgery for staging and/or cytoreduction followed by cisplatin 20 mg/m2 intravenously (IV) for 5 days and cyclophosphamide 600 mg/m2 on day 4 every 3 to 4 weeks for two to four cycles. Patients were then evaluated for IPT and, if eligible, had an intraperitoneal (IP) catheter placed. IPT consisted of cisplatin 60 mg/m2 in 2 L on day 1 and IV cyclophosphamide 600 mg/m2 on day 2 every 3 weeks for three to six cycles. Patients who demonstrated a clinical complete response (CCR) were then referred for second-look laparotomy (SLL). Of 71 patients who completed the induction phase, 53 (75%) were eligible for IPT, and 49 patients entered the therapy phase. Toxicity of the combined modality approach was acceptable and did not differ from our previous experience using the same drugs systemically. Thirty-two of the 49 patients who completed IPT achieved a CCR, which was confirmed by SLL in 20 patients. Twenty recurrences were documented in the 32 CCR patients, 13 occurred in patients after SLL. Projected median survival of all patients is 38 months. Median survival correlated with amount of residual disease following initial surgery (23 months for bulky v 45 months for minimal residual; P less than .001) and with performance status ([PS]; 24 months for PS 2, 3 v greater than 46 months for PS O; P less than .001). Patients who presented with bulky tumors were less likely to reach the consolidation IPT phase. Incorporation of IP cisplatin into the first-line regimen for treatment of ovarian cancer does not appear to have major impact on the survival of all treated patients when compared with our historical control series. Combined IV and IPT cisplatin and cyclophosphamide is feasible with acceptable toxicity. Its impact on response and survival may be limited to only "good-prognosis" patients.     

Combination chemotherapy with cisplatin, bleomycin, and methotrexate in patients with advanced head and neck cancer

Twenty-six patients with advanced head and neck cancer, 22 of whom had failed prior surgery and/or radiotherapy, were treated with a combination regimen of cis-diamminedichloroplatinum II, bleomycin, and methotrexate. There were no complete responses. Nine patients achieved a partial response (35%). Three of the four (75%) patients without prior therapy achieved a partial response while only 6 of the 22 patients (27%) with prior surgery and/or radiation therapy obtained a partial response. The median response duration was 3 months. Patients with a partial response did not live significantly longer than those who did not live significantly longer than those who did not respond. Toxic reactions were frequent: there were three episodes of sepsis secondary to leukopenia and two cases of bleomycin pulmonary toxicity. Mucositis was noted in 40% and nausea and vomiting in 60% of patients. We conclude that this triple-drug regimen has little value in the treatment of patients with advanced squamous cell carcinoma of the head and neck who have failed prior surgery and radiotherapy.     

Phase II studies of bleomycin, cyclophosphamide, doxorubicin and cisplatin, and bleomycin and cisplatin in advanced cervical carcinoma

In a randomized phase II trial of two cisplatin-based chemotherapy regimens, 45 patients with advanced cervical carcinoma received a combination of bleomycin, cyclophosphamide, doxorubicin, and cisplatin (BCAP), and 45 others received bleomycin plus cisplatin (BP). BCAP was repeated every 4 weeks, and BP was given at 3-week intervals. Although 19 of 43 (44%) evaluable patients receiving BCAP and 16 of 42 (38%) evaluable patients receiving BP experienced tumor regression, only 22% of those receiving BCAP and 21% of those on BP survived 1 year after beginning treatment. Among bidimensionally measurable patients, 15 of 27 (56%) and 8 of 25 (32%) receiving BCAP and BP, respectively, achieved tumor regression. One patient died of bleeding resulting from severe myelosuppression on BCAP, and two others succumbed to pulmonary toxicity of bleomycin on the BP regimen. Although active against cervical carcinoma, these regimens have limited therapeutic value at this advanced stage of the disease.     

晚期胃癌姑息性术后腹腔热灌注化疗联合静脉化疗与单纯静脉化疗的临床观察

目的:探讨晚期胃癌姑息性切除术后腹腔热灌注化疗联合静脉化疗的临床疗效及毒副反应。方法:65例晚期胃癌姑息性切除术后患者随机分为两组,治疗组34例采用术后腹腔热灌注化疗联合静脉化疗,对照组31例术后采用单一静脉化疗,对65例患者的临床资料作回顾性分析。结果:治疗组1、2、3年生存率分别为83.4%(28/34)、61.8%(21/34)、38.2%(13/34),对照组为90.3%(28/31)、32.3%(10/31)、16.1%(5/31),两组1年生存率比较无显著性差异(χ2=1.04,P>0.05),2、3年生存率比较有显著性差异(χ2=6.18,P<0.05;χ2=4.93,P<0.05);两组化疗毒副反应比较无显著性差异。治疗组存在的腹腔化疗并发症主要为腹痛、腹胀、腹泻、便秘。结论:晚期胃癌姑息性切除术后腹腔热灌注化疗联合静脉化疗在晚期胃癌的综合治疗中是一可取的治疗措施。     

丝裂霉素、长春花碱酰胺和顺铂联合治疗晚期肺腺癌

目的:评价丝裂霉素、长春花碱酰胺和顺铂联合治疗晚期肺腺癌的疗效和毒性.方法:32例不能手术的肺腺癌Ⅲ～Ⅳ期,MVP方案化疗:丝裂霉素6mg/m~2,静脉冲入,第1、8天;长春花碱酰胺2.5mg/m~2,静脉冲入,第1、8天;顺铂60～80mg/m~2,静脉滴注,第3天,水化.每3周为一周期,二周期后评价疗效.结果:部分缓解率(12/32)40.6%.毒副反应主要为恶心、呕吐和白细胞下降.结论:MVP方案是治疗晚期肺腺癌疗效较高的方案.     

Effective chemotherapy for advanced carcinoma of the cervix with bleomycin, cisplatin, vincristine, and methotrexate

This study was designed as a Phase II clinical trial in advanced recurrent or metastatic squamous cell carcinoma of the cervix with a combination of bleomycin (B: 10 u/m2/d) and cisplatin (P: 20 mg/m2/d) administered for five consecutive days in intravenous infusion for 7 hours and vincristine (V: 1 mg/m2) and methotrexate (M: 40 mg/m2) administered only on day one of each cycle which was repeated every 28 days up to a maximum of 6 times. Over a period of 2 years, 15 evaluable patients with measurable disease received at least 3 courses of therapy. Six had recurrent disease and nine had distant metastases. All had previous radiation therapy. There were two dropouts after the first course due to nausea and vomiting which was practically universal. Other side effects included: mild paresthesias of the extremities (89%), stomatitis (41%), diarrhea (17%), moderate pancytopenia and hypomagnesemia which was reduced from 65% to 17% when magnesium sulfate 10% was administered with cisplatin. Sixty-six percent of the evaluable patients achieved remission (7 partial and 3 complete) usually before the fourth course of therapy. The disease-free interval was of 29.7 +/- 15 weeks in all responders (40.6 +/- 15.5 weeks in complete responders). The mean survival from the start of BPVM therapy was of 55.8 +/- 33.3 weeks in responders and of only 14 +/- 2.9 weeks in nonresponders (P less than 0.01). It is concluded that BPVM is an effective combination chemotherapy in advanced squamous cell carcinoma of the cervix. These results should be confirmed in a Phase III trial.     

紫杉醇腹腔灌注化疗治疗晚期卵巢癌临床研究

目的：探讨紫杉醇（PTX）腹腔灌注化疗联合顺铂（PDD）全身化疗治疗晚期卵巢癌患者的疗效和安全性。方法：2006年1月至2010年1月,给予33例TNMⅢ-Ⅳ期卵巢癌患者（Ⅲ期20例,Ⅳ期13例）PTX60mg/m2ip d1,5,10,PDD 40mg/m2iv d1-2,每21天为1周期,共2-4个周期,每2周期评定疗效。结果：总有效率（RR,CR＋PR）为78.79%,其中CR 60.61%、PR 18.18%。中位疾病进展时间（TTP）为22.3个月。2年生存率为81.82%。常见不良反应为骨髓抑制、腹痛、腹泻、胃肠道反应、脱发、口腔黏膜炎和肌肉关节痛等。结论：PTX 60mg/m2腹腔灌注d1,5,10联合PDD 40mg/m2静脉滴注d1,2方案治疗晚期卵巢癌疗效肯定,且不良反应可以耐受。     

Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer

We report a phase II study of bleomycin, ifosfamide, and cisplatin (BIP) in cervical cancer. Our aims were to assess response rate, toxicity, and survival in women treated with this combination. Among 49 patients, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxic effects were assessed in 186 treatment cycles. All patients had alopecia and nausea and vomiting. Other effects included myelosuppression, infection, reduction in renal function, and disturbance of consciousness. These data indicate that BIP is highly active against advanced and recurrent cervical cancer.     

紫杉醇腹腔灌注化疗治疗晚期卵巢癌临床研究

目的 探讨紫杉醇(PTX)腹腔灌注化疗联合顺铂(PDD)全身化疗治疗晚期卵巢癌患者的疗效和安全性.方法 2006年1月至2010年1月,给予33例TNMⅢ-Ⅳ期卵巢癌患者(Ⅲ期20例,Ⅳ期13例)PTX 60mg/m2 ip d1,5,10,PDD 40mg/m2 iv d1-2,每21天为1周期,共2-4个周期,每2周期评定疗效.结果 总有效率(RR,CR+PR)为78.79%,其中CR 60.61%、PR 18.18%.中位疾病进展时间(TTP)为22.3个月.2年生存率为81.82%.常见不良反应为骨髓抑制、腹痛、腹泻、胃肠道反应、脱发、口腔黏膜炎和肌肉关节痛等.结论 PTX 60mg/m2腹腔灌注d1,5,10联合PDD 40mg/m2静脉滴注d1,2方案治疗晚期卵巢癌疗效肯定,且不良反应可以耐受.