Carboplatin/etoposide as first-line chemotherapy in advanced ovarian carcinoma: a pilot study

Summary In a pilot study, 18 patients with advanced ovarian cancer were evaluated for tolerance and response to a combination treatment with a fixed dose of carboplatin (350 mg/m² given i.v. on day 1) and escalated doses of etoposide (70–130 mg/m² daily given i.v. on days 1–3) as first-line chemotherapy. The maximum tolerated dose of etoposide was 130 mg/m² when given i.v. on days 1–3 in combination with 350 mg/m² carboplatin given i.v. every 4 weeks. At these dose levels, bone marrow toxicity was manageable and did not appear to be cumulative. In all, 12 objective responses, including 9 complete responses (CRs) and 3 partial responses (PRs), were achieved in 18 patients; 6 of the 9 CRs were confirmed as pathological CRs by second-look surgery.     

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。     

Combination chemotherapy in advanced ovarian carcinoma

Ovarian carcinoma is the fifth most common cause of death among women in western countries. It is often diagnosed in an advanced stage (FIGO Stage III and IV) and requires effective chemotherapy as first-line treatment. The advent of cis-platin combined with adriamycin and cyclophosphamide has remarkably increased the response rate in advanced disease. The authors report 31 cases of epithelial ovarian neoplasia, without prior chemotherapy, treated with cis-platin, adriamycin and cyclophosphamide (PAC I). Of the 30 evaluable patients, 15 had clinical complete remissions (cCR = 50%), 10 clinical partial remissions (cPR = 33%) and 5 no response (NR = 17%). The total response (cCR + cPR) was equal to 83%. Twelve of the 15 patients in cCR underwent second-look laparotomy; in 8 of these cases, histologic and cytologic confirmation of CR was obtained. PAC I was found to be a highly effective therapeutic regimen with moderate toxicity. The individual toxicity reported was gastroenteric (nausea and vomiting), but transitory. No chronic toxic side-effects from cisplatin or adriamycin were noted. However, more definitive results must be obtained to verify its impact on the prolongation of survival.     

Intraperitoneal high dose chemotherapy as consolidation treatment for advanced ovarian carcinoma: a pilot study]

Consolidation treatment of advanced ovarian carcinoma, especially the place of intraperitoneal chemotherapy, remains a controversial subject. From January 1988 to July 1995, 39 patients, median age 54 years, received intraperitoneal chemotherapy as consolidation treatment after second-look surgery. At the time of intraperitoneal chemotherapy, 30 patients had no residual disease. Intraperitoneal drug administration used a Tenckoff catheter or a lumbar needle. Treatment combined 5 fluorouracil 1 g/m2 and cisplatin 200 mg/m2, associated with a systemic sodium thiosulfate rescue as nephroprotector. A pharmacological analysis was done for 9 patients: the exposure of peritoneal cavity to cisplatin exceeded that of the plasma by 11 fold. Hematologic and nephrologic toxicity were acceptable. The median follow-up is 43 months. The disease free survival is 36,6 months, but 48,5 months if no residual disease at the time of intraperitoneal chemotherapy. Consolidation treatment by intense intraperitoneal chemotherapy is a feasible approach and might be beneficial in chemosensitive patients devoid of macroscopic remnants, but must be compared with others approaches.     

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.     

High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study

Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered.     

Combination chemotherapy for advanced colorectal cancer. A pilot study

Twenty-three patients with advanced colorectal carcinoma, mostly with liver and lung metastases and measurable disease, were treated with mitomycin-C 20 mg/m2 I.V. and vincristine 1.2 mg/m2 I.V. every 6 weeks, and cisplatinum 50 mg/m2 I.V. and 5-fluorouracil 1,000 mg/m2/24 hours I.V. continuous infusion for 96 hours every 3 weeks based upon the hypothesis that cisplatinum may potentiate the antitumor activity of antimetabolites and alkylating agents. Five patients had received prior chemotherapy and six had received prior radiotherapy, with one of these patients receiving both. One complete and 10 partial responses were observed, with an overall response rate of 48% (90% confidence interval 30-70%). The toxicity was manageable. A possible potentiating effect of cisplatinum is suggested in this first attempt in the treatment of colorectal cancer, and warrants further exploration.     

A randomized study of sequential versus alternating combination chemotherapy in advanced ovarian carcinoma

The concept of using either alternating or sequential combination chemotherapy with non-cross-resistant combinations was tested in a randomized trial including 301 previously untreated patients with advanced epithelial ovarian carcinoma. The sequential schedule consisted of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) followed by PH (cisplatin, hexamethylmelamine) in nonresponders, CAF- greater than PH (n = 157), and the alternating regimen consisted of CAF/PH (n = 144). With a median observation time of 54 months, no statistically significant differences were found between the pathologically complete response (PCR) rates of 17% and 16%, respectively, nor were there any statistical differences in median disease-free survival for PCR patients (CAF- greater than PH 34+ months and CAF/PH 26+ months), in overall survival (28 and 24 months, respectively), or in time to treatment failure (10 and 11 months). The overall estimated cure rate was 13%. An equal degree of myelosuppression was seen with the two regimens, whereas neuro- and nephrotoxicity were more pronounced when PH was given sequentially to CAF than with the alternating schedule. We conclude that the sequential and the alternated use of doxorubicin- and platinum-based regimens yield equivalent results and that other approaches should be investigated to improve treatment effects.     

热疗联合静脉及腹腔双路化疗治疗晚期胃肠道肿瘤临床观察

目的：探讨进展期胃肠癌应用热疗联合静脉及腹腔双路化疗治疗近期期疗效及不良反应。方法：1998年3月-2003年10月间收治进展期胃肠癌患者51例，分为静脉及腹腔双路化疗组及双路化疗联合热疗组，比较两组治疗疗效及术后毒副作用。结果：热疗联合静脉及腹腔双路化疗组近期有效率为56．5％，明显高于非热疗组32．1％（P〈0．05），两组不良反应类似。结论：热疗联合静脉及腹腔双路化疗效果显著，值得广泛应用。     

A phase I trial of intraperitoneal recombinant gamma-interferon in advanced ovarian carcinoma

The interferons are a class of biological agents that have demonstrated antineoplastic activity in a variety of tumors both in vitro and in vivo. Previous reports have suggested that interferons can be safely administered by the intraperitoneal (IP) route with a pharmacokinetic advantage for peritoneal cavity exposure compared with the systemic circulation and with objective antitumor activity being demonstrated. On the basis of these reports and laboratory data suggesting activity for recombinant gamma-interferon (r-GIFN) against several malignant cell lines, we treated 27 refractory ovarian carcinoma patients, including six with very-small-volume residual disease, with this agent delivered by the IP route. While r-GIFN was found to be remarkably well tolerated, with a 150- to 200-fold pharmacokinetic advantage for peak levels achieved in the peritoneal cavity compared with the plasma, no objective responses were observed. Despite the lack of demonstrated activity for single-agent IP-administered r-GIFN in this clinical setting, there remains considerable interest in this agent when delivered by the IP route because of in vitro data suggesting concentration-dependent synergy between r-GIFN and other biological agents.     

Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy

Ninety ovarian carcinoma patients failing primary intravenous (IV) combination chemotherapy were treated with cisplatin-based combination intraperitoneal therapy. Sixty-five patients had residual disease greater than 2 cm at the start of intraperitoneal therapy. Their median survival was 8 months. Twenty-five patients had disease less than 2 cm; their median survival was greater than 49 months, and the survival curve has an apparent plateau at 69%, with no relapses having occurred after 32 months. The median survival for all 90 patients was 15 months. The median duration of follow-up for all patients was 37 months. These results confirm the critical role of tumor bulk in determining the effectiveness of intraperitoneal therapy, and suggest a role for intraperitoneal salvage treatment in patients with small-volume disease.     

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。     

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.     

腹腔热灌注联合静脉化疗治疗晚期卵巢癌的疗效观察

目的:探讨晚期卵巢癌行腹腔热灌注联合静脉化疗的临床疗效及不良反应。方法:2008年12月-2012年12月收治 的100例晚期卵巢癌并大、中量腹腔积液患者采用信封法随机分为治疗组和对照组。治疗组60例,行腹腔热灌注联合静脉化疗;对照组40例,行单纯的静脉化疗。治疗组采用顺铂腹腔热灌注联合紫杉醇静脉化疗,对照组采用紫杉醇联合顺铂 静脉化疗,观察两组的腹水控制率及不良反应。结果:治疗组的腹水控制率为78.3%,对照组为42.5%,差异具有统计学 意义（P＜0.01）。两组的不良反应比较无统计学差异（P＞0.05）。结论:腹腔热灌注联合静脉化疗可有效的控制卵巢 癌患者恶性腹腔积液,不良反应能够耐受。     

Phase 2 study of intraperitoneal topotecan as consolidation chemotherapy in ovarian and primary peritoneal carcinoma

BACKGROUND: Intravenous topotecan is approved for the treatment of ovarian cancer (OC). In intraperitoneal (i.p.) topotecan studies, 20 mg/m(2) dosing was tolerable. This study evaluated the feasibility, safety, and preliminary efficacy of i.p. topotecan as consolidation chemotherapy in patients with OC or primary peritoneal cancers (PPCs). METHODS: Patients with stage III/IV ovarian or PPC in clinical complete response after surgical cytoreduction and intravenous carboplatin/paclitaxel chemotherapy who had benign findings or minimal persistent disease (< or = 1 cm diameter) at second-look surgery were eligible. Intraperitoneal topotecan 20 mg/m(2) was infused once every 21 days for 4 to 6 cycles. Kaplan-Meier estimates were used to calculate progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients were enrolled (18 [90%] patients had OC). Sixteen patients received 4 cycles, 3 patients received 6 cycles, and 1 patient withdrew after 1 cycle. The mean delivered dose was 18 mg/m(2). Grade 3/4 toxicities included neutropenia and thrombocytopenia (45% for both). Grade 1/2 abdominal distension and nausea were reported in 60% and 40% of patients, respectively. Median PFS was 24 months from second-look surgery (95% confidence intervals [CI]: +/-10 months). Sixteen patients were alive and median OS was not reached at the time of data analysis. OS estimated at either 30 months from second-look surgery, or 3 years from initial diagnosis, was 84% (95% CI, 68%-100%). CONCLUSIONS: Consolidation i.p. topotecan is a feasible option for women withadvanced ovarian and primary peritoneal cancers. Further investigation of i.p. topotecan is warranted in this patient population.     

Adjuvant whole-abdominal radiation therapy in uterine papillary serous carcinoma

Nine patients from 34 to 74 years of age (median, 67 years of age) with uterine papillary serous carcinoma (UPSC) were treated with whole-abdominal radiation therapy (WART) on an adjuvant basis after cytoreductive surgery. All patients were treated with megavoltage photons to an abdominopelvic field to a median dose of 2500 cGy, with continued treatment to a whole pelvic field to a median dose of 4500 cGy. Three patients received additional boost to the vaginal apex. Follow-up time ranged from 6 to 31 months (median, 25 months) after completion of WART. Six patients had recurrent disease at 5 to 20 months (median, 7.5 months). Four of these patients died of their disease during the follow-up period. Three of six patients in whom treatment failed had disease at the vaginal apex. None of these patients received boost radiation therapy to that site. In contrast, two of three patients remaining disease free were treated with additional vaginal apex irradiation. Based on these results, the authors do not routinely recommend WART for adjuvant treatment of UPSC. They do, however, recommend vaginal apex irradiation for these patients.     

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.     

Combination chemotherapy and immune capacity in advanced ovarian carcinoma

The effects of chemotherapy with either Chap-5 (a drug regimen consisting of adriamycin, cis-dichlorodiammine platinum (II), hexamethylmelamine and cyclophosphamide) or Hexa CAF (a drug regimen consisting of methotrexate, 5-fluorouracil, hexamethylmelamine and cyclophosphamide) on the immunocompetence of 22 patients with advanced ovarian carcinoma were studied. Both primary and secondary humoral and cellular immune responses in vivo were studied. In addition, the numbers of granulocytes, lymphocytes and monocytes in peripheral blood were determined, as well as the levels of immunoglobulins and complement proteins. Furthermore, the proliferative capacity of lymphocytes, cytotoxic T-cell function, and K- and NK-cell activities were measured. The results indicate a depression of the primary humoral immune response in vivo in patients receiving Chap-5. Furthermore, a decrease of several parameters in vitro was observed. However, these alterations were only moderate and rapidly reversible.     

晚期卵巢癌行热灌注化疗患者的生活质量现状分析

目的 调查晚期卵巢癌行热灌注化疗患者的生活质量。方法 采用一般资料调查问卷、生活质量核心问卷（QLQ-C30）、卵巢癌治疗功能评价量表（FACT-O）、自我感受负担量表（SPBS）、疼痛数字评价量表（NRS）及社会支持评定量表（SSRS）对本院300例晚期卵巢癌行热灌注化疗患者进行调查。结果 晚期卵巢癌行热灌注化疗患者QLQ-C30总分为（66.28±17.72）分,FACT-O 总分为（94.07±8.80）分,SPBS总分为（39.82±7.61）分;NRS评分为（5.68±1.24）分,SSRS得分为（23.96±6.57）分;Pearson相关分析结果显示,自我感受负担、社会支持和疼痛与生活质量相关（r=0.807,0.458,0.604）。结论 晚期卵巢癌行热灌注化疗患者的生活质量较差,自我感受负担、疼痛及社会支持可影响患者生活质量。