Treatment of Advanced or Recurrent Endometrial Carcinoma with Single-Agent Carboplatin

Cisplatin and the combination of cisplatin, doxorubicin, and cyclophosphamide have documented activity in women with advanced or recurrent endometrial adenocarcinoma. However, response duration has been short and toxicity is substantial. To determine if similar activity could be obtained with less morbidity, we prospectively treated 33 patients with 360 mg/m² carboplatin given intravenously every 28 days. Mean patient age was 69 years (range 40-86); all had a Zubrod functional status of 2 or less. Seventeen patients had advanced primary tumors, and 16 had recurrent disease. Prior treatment included surgical resection in 29 cases, hormonal agents in 7, and radiotherapy in 22. No patient had received prior chemotherapy. Mean treatment was 5.7 cycles. Nine of 27 patients (33%) with measurable disease had objective responses, including three complete and six partial responses. Nonresponders included 10 patients with stable disease and 8 whose disease progressed while on treatment. Median time to response was 3 months. Median progression-free survival for responders and nonresponders was 5 and 4 months, respectively. At analysis, 20 patients had died of disease, 7 were alive with disease, and 6 were clinically free of disease. Disease-free patients include 1 with a complete response and 5 who began treatment without measurable disease. Median follow-up for surviving patients was 18 months (range 4-32). Treatment toxic effects were minimal and largely limited to myelosuppression; 3 patients had grade 3 thrombocytopenia, 1 had grade 3 neutropenia, and 5 had grade 3 anemia. Carboplatin has definite activity in endometrial carcinoma and offers a well-tolerated palliative therapeutic alternative.     

A phase II evaluation of tirapazamine plus cisplatin in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study

OBJECTIVES: To estimate the anti-tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancers. METHODS: Eligible consenting patients had to have recurrent epithelial ovarian or primary peritoneal carcinoma with measurable disease. Patients were not allowed to have received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens. Patients must have been platinum-sensitive, meaning a treatment-free interval of >6 months after response to a platinum-based regimen. The RECIST criteria were used for parameters of response. Tirapazamine was administered at a dose of 390 mg/m2 IV over 2 h followed 1 h later by cisplatin 60 mg/m2 IV every 3 weeks until disease progression or adverse effects prohibited further therapy. RESULTS.: Between June 2001 and February 2004, 65 patients were entered onto this study by 27 institutions; one patient was excluded due to ineligible tumor type. Twenty-six patients (41%) received six or more cycles of therapy; however, 16 (25%) received one course of therapy (mainly due to side effects or patient request). There were six (9%) complete responders and 28 (44%) partial responders for a total response rate of 53%. Only two patients (3%) developed increasing disease on this protocol, and response could not be assessed in 18 patients (28%). The median progression-free and overall survival for all patients is 10.9 and 26.4 months, respectively. The regimen did not cause major hematologic toxicity, however, it did cause frequent constitutional (23%) and gastrointestinal (mostly nausea/vomiting) (44%) grade 3 or 4 toxicity. CONCLUSIONS: The combination of tirapazamine and cisplatin has definite activity in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer. However, toxicity, primarily non-hematologic, was substantial. Reducing the toxicity of a tirapazamine-platinum combination should be pursued in future trials.     

Second-line with paclitaxel and carboplatin for recurrent disease following first paclitaxel and platinum compounds in ovarian carcinoma

OBJECTIVE: The combination of paclitaxel and platinum compounds is considered the best first-line regimen for advanced ovarian carcinoma. The purpose of this study was to evaluate a paclitaxel and carboplatin combination in pretreated patients who recurred within 24 months after a complete clinical response with the same regimen used as first-line chemotherapy. METHODS: 18 patients were included in this study. Second-line chemotherapy consisted of paclitaxel, 175 mg/m2 as a 3-hour infusion, and carboplatin AUC 6 every 21 days. RESULTS: Among 15 evaluable patients, eight (53%) complete and five (34%) partial responses were observed, while two (13%) patients had stable disease (SD). The response rate was 67% among patients with measurable disease and 52% for evaluable disease. The median progression-free interval after second-line chemotherapy was 8.3 months. The median progression-free interval for patients with measurable disease was 8.6 months and for evaluable disease it was 7.9 months. Seven (46%) of 15 patients have developed recurrence after second-line chemotherapy with paclitaxel and carboplatin with a median time to recurrence of 9.8 months. CONCLUSION: Paclitaxel 175 mg/m2 and carboplatin AUC 6 as second-line chemotherapy in this sensitive population is effective in terms of response rate and progression-free interval.     

Cervical non-squamous carcinoma: an effective combination chemotherapy of taxane, anthracycline and platinum for advanced or recurrent cases

Objective

An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.

Study design

This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.

Results

Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1–108) and 13 months (5–108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p < 0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).

Conclusion

Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity.     

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.     

Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1-13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.     

The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study

OBJECTIVES: To explore associations between histology and outcome in advanced or recurrent endometrial cancer patients participating in Gynecologic Oncology Group chemotherapy trials. METHODS: Age, race, performance status, histologic type (serous=S; clear cell=CC; endometrioid=E), disease stage, and prior radiation were evaluated using various analytic methods to evaluate the probability of response and identify independent predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: Single agent or combination chemotherapy regimens including doxorubicin (A) (12%), doxorubicin/cisplatin (AP) (63%), doxorubicin/paclitaxel (AT) (13%), and paclitaxel/doxorubicin/cisplatin (TAP) (11%) were used among 1203 patients treated on 4 randomized clinical trials. Breakdown of disease stage was 7.8% stage III, 22.8% stage IV, and 69.4% recurrent disease. Histologic distribution was 18% S, 3.7% CC, 8.5% mixed, 51.7% E and 18.1% other. More S/CC patients enrolled on trials with advanced stage (III-IV) disease (as opposed to recurrent disease) compared to E patients (45% vs. 24%, p<0.05). Overall response rate was 42% (E=44%, S=44%, CC=32%). Histologic type was not an independent predictor of response. Independent predictors of PFS included race, performance status, disease stage, and CC histology. Histology was also an independent predictor of OS; the relative hazard ratio for S histology was 1.2 (1.02-1.4; p=0.03), and for CC was 1.51 (1.1-2.07; p=0.01). CONCLUSION: In patients with advanced/recurrent endometrial cancer treated with A, P and/or T, response was not associated with histology. This exploratory analysis does not support exclusion of S tumors in future trials. Poorer PFS and OS were observed in CC compared to other types, but a lack of benefit from chemotherapy was not shown, and as this histology represents such a small fraction, it does not seem feasible to have separate chemotherapy trials for CC.     

Phase II clinical study of irinotecan and cisplatin as first-line chemotherapy in metastatic or recurrent cervical cancer

OBJECTIVE: The goal of this study was to evaluate the efficacy and tolerability of irinotecan plus cisplatin as first-line chemotherapy in metastatic or recurrent cervical cancer. METHODS: Chemotherapy-naive patients with metastatic or recurrent disease and at least one measurable tumor site received irinotecan (60 mg/m(2) IV infusion over 90 min) on Days 1, 8, and 15, followed by cisplatin (60 mg/m(2) IV over 90 min) on Day 1, every 28 days for a maximum of six cycles. RESULTS: Thirty patients were included in the response and toxicity analysis. The median age was 45 years (34-65). Nineteen patients had metastatic disease, 6 presented with locally recurrent disease, and 5 presented with locally recurrent plus metastatic disease. Seven patients were stage IVB at diagnosis. There were 2 complete and 18 partial responses and overall response rate was 66.7% (95% confidence interval: 47-85%). Stable disease was observed in 2 patients (6.7%) and progression in 8 (26.7%). Median time to relapse was 13.4 months, with a median survival time of 16.9 months. One-year disease-free survival and overall survival were 26.7 and 65.1%, respectively. Dose-limiting toxicity was observed in 4 patients (13.3%) with grade 3 renal toxicity. Nine patients (30%) developed grade 3 neutropenia, and only grade 1-2 acute and late diarrhea were observed in 20 and 40%, respectively. A patient developed pancolitis after the sixth cycle. There were no chemotherapy-related deaths. CONCLUSION: The combination of irinotecan and cisplatin is a clinically active regimen for metastatic and/or recurrent cervical cancer with acceptable tolerability.     

Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m²), doxorubicin (50 mg/m²), and cyclophos-phamide (500 mg/m²) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1–13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.     

Treatment of advanced uterine sarcoma with vincristine,actinomycin D,and cyclophosphamide

Between 1971 and 1979, seventy-four patients with metastatic or advanced recurrent sarcoma of uterine origin were treated with combination chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide (Cytoxan). The probability of survival at 2 and 5 years was 23 and 15%, respectively. The response rate for patients with measurable disease was 28.9% (15.6% partial responses and 13.3% complete responses). The median duration of a complete response was 16 months and that of a partial response was 5.5 months. The median survival of the complete responders was prolonged when compared to nonresponders.     

原发性腹膜恶性肿瘤化疗方案的探讨

目的 比较原发性腹膜恶性肿瘤采用不同化疗方案治疗对患者生存时间的影响。方法 对1995年5月．2005年5月在本院治疗的27例原发性腹膜恶性肿瘤患者的临床病理资料进行回顾性分析。结果 全部患者均施行肿瘤细胞减灭术，术后予以铂类为主的方案化疗。24例患者采用TP（紫杉醇＋顺铂／卡铂）或PAC（顺铂＋阿霉素＋环磷酰胺）方案化疗，其中2例失访，2例尚未完成化疗；另有2例患者采用以铂类为主的其他方案化疗，1例未化疗。总结有完整化疗及随访资料的20例患者的生存情况。TP方案组13例，PAC方案组7例。20例患者初次化疗缓解率80％（完全缓解60％，部分缓解20％），无进展中位生存时间16个月（11。21个月），总体中位生存时间42个月（22．3～61．7个月）。TP方案组和PAC方案组患者的年龄、绝经状况、腹水细胞学检查、手术后残余灶大小、手术分期（沿用卵巢癌FIGO分期标准）、病理类型、化疗疗程及化疗毒副反应均无统计学差异。TP方案组患者无进展中位生存时间19个月，PAC方案组12个月，两者比较无统计学差异；TP方案组和PAC方案组患者的平均生存时间分别为69个月和28个月，两者比较，差异有统计学意义（P〈0．05）。结论 原发性腹膜恶性肿瘤采取肿瘤细胞减灭术及铂类为主的化疗方案可改善预后，TP联合化疗可能优于PAC方案延长患者生存时间。     

卵巢上皮性癌血清肿瘤标志物谱变化的临床意义

目的 探讨卵巢上皮性癌(卵巢癌)患者化疗后肿瘤标志物谱的变化及其潜在的临床意义.方法 选择1999年1月至2007年7月期间经肿瘤细胞减灭术及规范化疗的卵巢癌患者102例,对其术前、术后、每次化疗前、随访期间和复发前后的血清肿瘤标志物CA125、CA19-9和CP2的水平进行检测、分析,其中48例患者的肿瘤标志物记录完整而纳入分析,复发患者为28例,初治化疗患者20例(均为耐药病例).根据肿瘤标志物谱变化与否,分别将复发和初治化疗患者分为肿瘤标志物谱变化组与未变化组.平均随访时间为25个月.结果 (1)肿瘤标志物谱的主要变化表现为标志物的数最变化和(或)标志物的种类改变.28例复发患者中肿瘤标志物谱发生变化者占46%(13/28),20例初治化疗患者中标志物谱发生变化者占45%(9/20).(2)肿瘤标志物谱变化的复发患者中,病理类型以浆液性癌所占比例最高,为77%(10/13),而初治化疗患者中,以黏液性癌所占比例最高,为4/9.(3)复发患者肿瘤标志物谱变化组的无疾病进展期和中位总生存时间分别为22.2、60.0个月,较未变化组(分别为17.4、46.0个月)明显延长(P均<0.05);初治化疗患者肿瘤标志物谱变化组的中位总生存时间较未变化组(分别为15.9、25.0个月)明显缩短(P<0.05).结论 卵巢癌化疗期间和复发后肿瘤标志物谱可发生变化,化疗及随访期间应对肿瘤标志物进行联合检测.     

Combination cisplatin and dichloromethotrexate in patients with advanced or recurrent cervical cancer: a preliminary report

The chemotherapy combination of cisplatin and dichloromethotrexate was administered to 14 patients with measurable cervical cancer. Six (46%) have had a complete response for 6+, 7, 11, 14, 15, and 21 months. Four (30%) have had a partial response for 1, 6, 10, and 11 months. Two patients (15%) have had stable disease for 6 and 11 months. Only one patient failed to respond to this combination. In six of these patients, the measurable mass was located in a previously radiated area. This combination was well tolerated with only three instances of severe toxicity. No irreversible renal dysfunction was seen in any patient.     

原发性腹膜恶性肿瘤的治疗及预后分析

目的 探讨原发性腹膜恶性肿瘤的临床治疗方案及预后相关因素。方法 对1995年5月—2004年4月在北京大学人民医院治疗的24例原发性腹膜恶性肿瘤患者的临床病理资料进行回顾性分析。结果 24例患者中,腹膜浆液性乳头状腺癌15例(中、高分化9例,低分化6例),腹膜混合型上皮性癌6例,腹膜恶性苗勒管混合瘤3例。全部患者均施行肿瘤细胞减灭术,其中满意的肿瘤细胞减灭术(残留灶直径＜2cm)3例,不满意的肿瘤细胞减灭术(残留灶直径≥2cm)21例。术后给予以铂类为主的联合化疗,其中13例行紫杉醇 顺铂或卡铂(TP)方案化疗,9例行顺铂 阿霉素 环磷酰胺(PAC)方案化疗。初次化疗缓解率为80％,其中完全缓解率为55％,部分缓解率为25％。患者的中位数生存时间为42个月(22～62个月),其中腹膜浆液性乳头状腺癌、恶性苗勒管混合瘤、混合型上皮性癌患者的中位数生存时间分别为44、13和19个月,前两者比较,差异有统计学意义(P＜0．05),而后者分别与前两者比较,差异均无统计学意义(P＞0．05);接受,TP和PAC方案化疗患者的平均生存时间分别为75、28个月,两者比较,差异有统计学意义(P＜0．05)。结论 原发性腹膜恶性肿瘤的治疗,应尽量首选恰当的肿瘤细胞减灭术,基本术式为双侧附件及大网膜切除术,过分强调减瘤的彻底性可能不利于患者的预后;术后应给予以铂类为主的联合化疗,TP方案可能优于PAC方案。病理类型及化疗方案是预后的影响因素。     

Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer

OBJECTIVE: To investigate tumor response rate and treatment toxicity of a modified combination chemotherapy consisting of bleomycin (B), methotrexate (M), and CCNU (C) for patients with locally advanced, squamous-cell carcinoma of the vulva (not amenable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reassessed in patients who had responded to chemotherapy. METHODS: The regimen consisted of bleomycin 5 mg intramuscular (im) days 1-5, CCNU 40 mg per os (po) days 5-7, and methotrexate 15 mg po days 1 and 4 during the first week. During weeks 2-6 the patient was administered bleomycin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. This 6-week cycle was repeated at 49-day intervals. RESULTS: Twenty-five eligible patients with a median age of 66 years (range, 39-82 years) were entered in this phase II trial. Twelve patients had primary locally advanced disease, 13 patients had a locoregional recurrence, and all received up to three BMC cycles. Two complete and twelve partial responses were observed (response rate, 56%; 95% confidence limits, 35-76%). The BMC regimen was associated with major hematological side effects and mild signs of bleomycin-related pulmonary toxicity. At a median follow-up of 8 months, 3 patients were alive, 18 had died due to malignant disease, 2 had died due to toxicity, and 2 had died due to intercurrent disease and unknown cause. The median progression-free survival was 4.8 months and the median survival was 7.8 months. The 1-year survival was 32% (95% confidence limits, 13-51%). CONCLUSION: The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squamous-cell carcinoma of the vulva. Following neoadjuvant chemotherapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of advanced or recurrent vulva cancer.     

Treatment of advanced epithelial ovarian cancer with cisplatin and cyclophosphamide

Between June 1981 and June 1984, 50 patients with stage III or IV epithelial ovarian cancer underwent initial surgery followed by combination chemotherapy with cisplatin 50 mg/m2 iv and cyclophosphamide 500-1000 mg/m2 iv at 28-day intervals. No patients with borderline or well-differentiated tumors were included. If patients were clinically disease-free after 12 cycles of therapy, a second-look laparotomy was performed. A complete response was noted in 12 patients (24%), 11 of whom were surgically evaluated. A partial response was noted in 4 patients (8%), 3 of whom were surgically evaluated. Thirty-four patients (68%) had no response to therapy. The median progression-free survival (PFS) for the entire group was 19.8 months, with a median survival of 27 months. Patients with less than or equal to 2 cm residual disease had a superior median PFS (25.4 months vs 18 months) and median survival (29.4 months vs 19.5 months) to those patients with greater than 2 cm residual disease. Patients who underwent primary debulking had a longer median survival than patients who underwent "interval" debulking after two to four cycles of chemotherapy (29.2 months vs 17.3 months). Thirteen patients (26%) are alive without evidence of disease, 4 patients are alive with disease, and 33 patients are dead of disease. Toxicity was very moderate. In summary, the activity and toxicity of the combination of cisplatin and cyclophosphamide compare favorably to other cisplatin combination regimens.     

A pilot study of weekly docetaxel therapy for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer

We investigated the efficacy and toxicity of salvage chemotherapy with weekly docetaxel for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer after treatment with regimens containing platinum or paclitaxel. The 15 subjects were managed as outpatients and received at least two courses of docetaxel therapy (35 mg/m2 on days 1, 8 and 15). Antitumour activity was assessed radiologically and from the CA-125 level. Among five patients with measurable lesions, one showed partial remission and three showed stable disease. Based on CA-125 levels, there were three partial remissions and five patients with stable disease (progression-free survival was 7.5 months and 7.6 months, respectively). During 61 courses, the severe toxicities were grade 3 leukopaenia/neutropaenia (6.7%) or grade 2 oedema and pleural effusion (13.3%). Weekly docetaxel may be useful salvage chemotherapy for recurrent ovarian cancer, tubal cancer, and peritoneal cancer, especially as tumour dormancy therapy.     

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.     

Combination chemotherapy for patients with advanced carcinoma of the cervix: trial of mitomycin-C, vincristine, bleomycin, and cisplatin

Sixteen patients with metastatic or recurrent carcinoma of the cervix were treated with combination chemotherapy consisting of mitomycin-C, vincristine, bleomycin, and cisplatin. Seven of 14 (50%) evaluable patients responded. In 2 patients all measurable disease resolved. Median duration of response was 4.5 months. Toxicity was severe and consisted of myelosuppression, pulmonary fibrosis, nausea, vomiting, stomatitis, asthenia, and fever. Two treatment-related deaths occurred. This combination chemotherapy regimen appears to have a response rate similar to other cisplatin containing regimens. Response durations were short and toxicity was severe.     

Radiation treatment of advanced or recurrent granulosa cell tumor of the ovary

BACKGROUND: Because granulosa cell tumors of the ovary are rare, the optimal treatment for women with gross residual disease after primary surgery or recurrence is not known. Our objective was to review the results of radiotherapy for advanced or recurrent granulosa cell tumor of the ovary. METHODS: This retrospective review identified 34 patients with ovarian granulosa cell tumors treated with radiation at the University of Texas M. D. Anderson Cancer Center between 1949 and 1988. Fourteen received treatment for clinically measurable disease; 20 received adjuvant radiotherapy after surgery for minimal residual (<1 cm) or microscopic residual disease. The 14 patients with measurable disease formed the basis for this review. RESULTS: Ten of 14 patients were treated with moving-strip whole-abdomen radiation (27-28 Gy), 9 with 60Co, and 1 with 6-MeV photons and a pelvic boost of 28 Gy with 22-25 MeV photons. The other 4 patients were treated with pelvic radiotherapy (45-61 Gy) with 22-25 MeV photons. Six of 14 patients (43%) had a clinical complete response to radiotherapy, with a median follow-up of 13 years (range, 5-21 years). Three of 6 who responded to radiation had relapse 4-5 years later; 2 of these 3 died of disease and 1 was alive with disease at last follow-up. Three responders remain alive without evidence of disease 10-21 years after treatment. The 8 nonresponders had a median survival of 12.3 months (range, 1-60 months). CONCLUSIONS: Radiotherapy can induce a clinical response with occasional long-term remission in patients with persistent or recurrent granulosa cell tumor of the ovary.