Cisplatin, vincristine, methotrexate and bleomycin (POMB) as initial or palliative chemotherapy for carcinoma of the cervix

Summary. Chemotherapy was given as initial therapy to 12 women with very advanced squamous cell carcinoma of the cervix and to 19 women with recurrent disease. They received a median of four courses of POMB which comprised vincristine 1.0 mg/m2 and methotrexate 300 mg/m2 followed by folinic acid rescue, bleomycin 30 mg as a 48-h infusion or intramuscular injection and cisplatin 100 mg/m2 as a 12-h infusion. Two of the 14 assessable patients with recurrent disease (14%) had a complete response with no disease found histologically in one, and seven (50%) had a partial response. Although the actuarial median survival of all 19 patients with recurrent disease was 8 months, five patients have remained free from tumour progression for a median of 17 months from start of chemotherapy. Six of the 10 assessable patients receiving initial chemotherapy (60%) had a complete response (confirmed histologically in two) and two (20%) had a partial response. Nine patients had additional treatment with radiotherapy and or surgery. Although only four of the patients remain disease-free at 61, 51, 7 and 4 months, all but two were initially FIGO stage IV. Although cisplatin-induced emesis is controllable and the side-effects of methotrexate can be avoided, the POMB regimen remains potentially toxic. The small number of patients with very advanced disease who are long-term survivors prompts us to study further the role of aggressive chemotherapy as the initial treatment of patients with visceral or nodal involvement from carcinoma of the cervix.     

Cisplatin, vincristine, methotrexate and bleomycin (POMB) as initial or palliative chemotherapy for carcinoma of the cervix

Chemotherapy was given as initial therapy to 12 women with very advanced squamous cell carcinoma of the cervix and to 19 women with recurrent disease. They received a median of four courses of POMB which comprised vincristine 1.0 mg/m2 and methotrexate 300 mg/m2 followed by folinic acid rescue, bleomycin 30 mg as a 48-h infusion or intramuscular injection and cisplatin 100 mg/m2 as a 12-h infusion. Two of the 14 assessable patients with recurrent disease (14%) had a complete response with no disease found histologically in one, and seven (50%) had a partial response. Although the actuarial median survival of all 19 patients with recurrent disease was 8 months, five patients have remained free from tumour progression for a median of 17 months from start of chemotherapy. Six of the 10 assessable patients receiving initial chemotherapy (60%) had a complete response (confirmed histologically in two) and two (20%) had a partial response. Nine patients had additional treatment with radiotherapy and or surgery. Although only four of the patients remain disease-free at 61, 51, 7 and 4 months, all but two were initially FIGO stage IV. Although cisplatin-induced emesis is controllable and the side-effects of methotrexate can be avoided, the POMB regimen remains potentially toxic. The small number of patients with very advanced disease who are long-term survivors prompts us to study further the role of aggressive chemotherapy as the initial treatment of patients with visceral or nodal involvement from carcinoma of the cervix.     

Endometrial carcinoma: Steroid receptors and response to medroxyprogesterone acetate

The steroid receptor content of the primary endometrial cancer of 22 patients who were treated for recurrent or advanced disease has been measured and correlated with response to medroxyprogesterone acetate. No patient with a progesterone receptor (PR)-negative tumor responded and only 2 patients with PR-positive tumors responded, perhaps related to the low levels of PR in the tumors. It waits to be assessed whether receptor status is as good a guide to response to hormone therapy as tumor differentiation, site of recurrence, or disease-free interval.     

Studies of intra-arterial hypertensive chemotherapy with cisplatin and peplomycin in advanced cancer of the uterine cervix--suitable dose of angiotensin II determined by intra-arterial digital subtraction angiography

We have been treating advanced cancer of the cervix uteri with intra-arterial cisplatin (CDDP) and peplomycin (PEP) (injected into the bilateral internal iliac artery), combined with radiotherapy and hysterectomy. Concomitant angiotensin II (ATII) administered by intravenous drip infusion was found to double tumoral blood flow and thereby to enhance the efficiency of the intra-arterial chemotherapeutic regimen. In the present study, hypertensive intra-arterial chemotherapy utilizing ATII was administered to a small group of patients with advanced cancer of the cervix uteri while ascertaining the increase in intratumoral blood flow by intra-arterial digital subtraction angiography. The subjects were 10 patients with stage IIb or more advanced cancer of the cervix uteri. Results: A 2-fold or greater increase in tumoral blood flow was attained in those patients who showed concurrently a 1.5 fold or greater increase in mean blood pressure and an increase in mean blood pressure to 150mmHg or higher. In 2 patients, ATII infusion failed to raise blood pressure to a therapeutically adequate level. At 1 week after the treatment in question histological evidence indicated unequivocal degenerative changes and necrotic changes in tumor cells. Many plasma cells, lymphocytes + and granulocytes appeared around necrosis changed carcinoma nests.     

Fundamental studies on arterial infusion chemotherapy for cervical cancer--with reference to the histological finding in infiltrating cancer and localization of the drugs in tissues

Preoperative arterial infusion of peplomycin was carried out on 15 cases of Stage I or II cancer of the cervix, and the value of arterial infusion chemotherapy with peplomycin and its efficacy as a preoperative therapy in cervical cancer were evaluated by analysis of (1) histological changes, (2) localization of the drug in tissue, and (3) tissue concentration of the drug in the completely resected tissues, with the following results: The chief histological change was a regression of cancer nests accompanied by degeneration and necrosis of cancer cells. This change was clearer at the head of infiltrating cancers than at their superficial layer or center. Peplomycin was localized with high activity at the disintegrated part of cancer nests, i.e., its activity was closely correlated to the severity of histological change. Time-course changes in its localization suggested the vessel wall----stroma----cancer as the route of its transport. The tissue concentration of peplomycin was maintained high over a long time. Particularly in the portio vaginalis, the time course decline of the concentration was gentle. From the above findings, arterial infusion of peplomycin was considered to be an effective method of chemotherapy for cervical cancer, and worth being tried as a preoperative therapy too.     

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.     

Phase II trial of vinorelbine in recurrent and progressive epithelial ovarian cancer

OBJECTIVE: A phase II, multicenter trial was conducted to define the efficacy and safety of vinorelbine (Navelbine (vinorelbine tartrate) injection, NVB) in the treatment of advanced epithelial ovarian cancer (EOC). METHODS: Patients with persistent or recurrent EOC who had received one prior platinum-based chemotherapy regimen were eligible. NVB was administered at 30 mg/m2 as a weekly outpatient intravenous infusion. RESULTS: Using an intent-to-treat analysis of the 38 patients who received at least one dose, 11(29%, 95% confidence limits 15-46%) objective responses (4 complete, 7 partial) were observed. The median duration of response was 19 weeks. For all 38 patients, the median time to treatment failure and median survival were 12 and 60 weeks, respectively. Four of the 12 patients with platinum-resistant disease responded, while 7 of the 24 patients with platinum-sensitive disease responded. Toxicity was evaluable in all 38 patients. During course 1, 15 patients required dose reduction and 21 required dose delays. Grade 3-4 granulocytopenia occurred in 23 (62%) of 37 reporting patients. Grade 3-4 anemia and thrombocytopenia occurred in 16 and 5%, respectively. The most common nonhematologic toxicities were nausea (grade 3 or less, in 34%), constipation (grade 3 or less, in 29%), and asthenia (grade 2 or less, in 24%). No life-threatening adverse effects were reported. CONCLUSIONS: NVB is an effective, palliative agent for women with recurrent EOC. Dose-limiting granulocytopenia is substantial, yet manageable.     

A phase II trial of arzoxifene,a selective estrogen response modulator,in patients with recurrent or advanced endometrial cancer

OBJECTIVES: The goal of this study was to determine response rate and evaluate toxicity of LY353381 (arzoxifene) in patients with recurrent or advanced endometrial cancer (EC). METHODS: A phase II, open-labeled study with arzoxifene was performed at 13 centers. Patients with measurable recurrent/advanced EC not amenable to curative therapies were eligible if either the primary tumor or recurrent tumor was ER+ and/or PR+. If receptor status could not be determined, patients with well or moderately well-differentiated EC were also permitted. Prior use of salvage chemotherapy was not allowed; however, prior use of progestagens was permitted and patients were stratified by prior exposure to progestagen. Patients received 20 mg/day PO, and were treated for at least 8 weeks in the absence of disease progression or unacceptable toxicity. Efficacy was based on the frequency of complete (CR) and partial (PR) responses, and a 95% confidence interval (CI) was calculated. The Kaplan-Meier method was used to analyze time to progression and duration of response. RESULTS: From February 1999 through April 2001, 37 patients were entered of whom 34 received treatment. Efficacy was evaluated for the 29 patients who received at least 4 weeks of therapy and at least one tumor response assessment. Safety was assessed in all 34 patients who received any drug. Thirty patients were defined as progestagen sensitive, and 4 patients were defined as progestagen failures. Twenty-six patients were ER+, and 22 were PR+. Nine (1 CR + 8 PR) of 29 patients responded (31%, CI 25-51%), with a median duration of response of 13.9 months. All 9 responses occurred in progestagen-sensitive patients. Two additional patients (one from each progestagen cohort) had stable disease for >or=6 months. The median progression-free interval was 3.7 months (CI 1.9-6.6 months) for all 29 patients. Toxicity was minimal with no grade 3-4 toxic effects, and 9 patients had only grade 1-2 toxic effects (7 grade 1, 2 grade 2). Hot flashes were the most common toxic effect and, in all 3 reported cases, were grade 1. CONCLUSIONS: Arzoxifene has demonstrated a high response rate with the longest median duration of response reported in a phase II trial of this patient population. The ease of administration and extremely favorable toxicity profile make this an agent warranting further evaluation.     

Treatment of uterine papillary serous carcinoma with paclitaxel.

OBJECTIVE: The aim of this study was to determine the effectiveness and toxicity of monthly treatment with intravenous paclitaxel for women with advanced or recurrent uterine papillary serous carcinoma (UPSC). METHODS: Consenting women with histologically confirmed advanced (FIGO stage III or IV) or recurrent UPSC were treated on an Institutional Review Board approved protocol of a 24-h intravenous infusion of 200 mg/m(2) of paclitaxel every 3 weeks. Both measurable and nonmeasurable disease cases were enrolled. Treatment was continued until disease progression, patient intolerance, or (in women with nonmeasurable disease) completion of six courses. RESULTS: Twenty patients received from 1 to 11 cycles of therapy. Two women died of disease after 1 cycle of therapy and were not evaluable for response. Among 13 women with measurable tumor receiving 2 or more cycles of therapy, 4 had a complete clinical response and 6 had a partial response (objective response rate, 77%). The median time to progression was 7.3 months (range, 2-21 months). All 3 remaining patients with measurable disease had stable disease for a median of 6 months. The 5 patients without evaluable disease received 5 to 6 cycles of adjuvant paclitaxel. Three developed recurrence (range, 4-10 months; median, 7.2 months). Neutropenia was the major toxicity. Eleven of the 20 patients required G-CSF support, and 9 were hospitalized for neutropenic fever. One woman had reversible cardiac symptoms, which might have been related to paclitaxel treatment. At the time of analysis (mean follow-up, 23 months; range, 4.3-59.9 months), 13 women had died of disease, 4 were alive with disease, and 2 were disease free. All 3 disease-free patients had been treated for nonmeasurable advanced stage disease. CONCLUSION: Paclitaxel appears to have excellent activity in the treatment of advanced or recurrent UPSC, an uncommon but aggressive malignancy. Longer survival appears to be more common among women with small-volume disease.     

Bleomycin, Methotrexate, and CCNU in Locally Advanced or Recurrent, Inoperable, Squamous-Cell Carcinoma of the Vulva: An EORTC Gynaecological Cancer Cooperative Group Study

Objectives. 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 with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma

OBJECTIVES: The goal of this study was to evaluate the efficacy and toxicity of paclitaxel plus carboplatin in the treatment of primarily advanced or recurrent endometrial carcinoma. METHODS: Thirty-seven consecutive patients with advanced or recurrent endometrial carcinoma were enrolled in this study. Paclitaxel at a dose of 175 mg/m(2) was administered intravenously over 3 h followed by carboplatin with area under the curve of 5 to 6 over 1 h at 4-week intervals. Five patients were received 50 Gy pelvic irradiation, and 7 were received 50 Gy pelvic and 50 Gy paraaortic irradiation, after adjuvant chemotherapy with paclitaxel plus carboplatin. Eighteen patients had evaluable lesions. Responses were assessed before the use of any irradiation. RESULTS: Eleven patients (61%) achieved an objective response, including one complete response (5.6%) and 10 partial responses (56%). The most common toxicity was hematologic: grade 3 or 4 leukopenia and neutropenia occurred in 59% and 86% of patients, respectively. Three patients (8%) required granulocyte colony-stimulating factor support. One patient required a platelet transfusion, and four required blood transfusions. There was a single adverse event of anaphylaxis. CONCLUSION: The combination of paclitaxel and carboplatin appears to be an effective regimen for the treatment of patients with advanced or recurrent endometrial carcinoma with tolerable toxicity.     

Bleomycin, vincristine, mitomycin-C, and cisplatin in the management of gynecological squamous cell carcinomas

Twenty-one patients with squamous carcinoma of the genital tract were treated with bleomycin, Oncovin, mitomycin-C, and cisplatin (BOMP). Six patients received BOMP as primary therapy. Five of six responded with one patient having an autopsy-proven complete response after treatment for a disseminated adenosquamous carcinoma. Eight patients were treated for early recurrence, none responded. Seven patients were treated for late recurrences and one responded. We believe that BOMP has significant potential for primary treatment, but not for early or late recurrent disease.     

A phase II study of gemcitabine and cisplatin in patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix

OBJECTIVE: The aim of this study was to determine the response rate and toxicity of cis-platinum and gemcitabine in advanced, recurrent, or persistent squamous cell carcinoma of the cervix. METHODS: From July 1997 to January 1999, we conducted a Phase II trial in patients with advanced, persistent, or recurrent carcinoma of the cervix. The schedule employed 1250 mg/m(2) of gemcitabine on days 1 and 8 and 50 mg/m(2) of cis-platinum on day 1 in a 21-day cycle. Eligibility criteria were a GOG performance status of 0-2, adequate bone marrow reserve, serum creatinine less than 1.8 mg%, and a lesion which could be measured in two dimensions. None of the patients had received prior chemotherapy other than radiation sensitizers. Standard GOG toxicity and response criteria were used. RESULTS: Nineteen patients were enrolled into the trial. Two patients were inevaluable because of inadequate trial of drug. Seventeen patients were evaluable for response and toxicity. The median age of the patients was 47 years (range 24-72). The median number of cycles delivered was 5 (range 2-8). The incidence of grade 4 neutropenia and anemia was 2.4 and 1.2%, respectively. Two patients developed a single episode of grade 3 gastrointestinal toxicity. The overall response rate was 41% (7/17). There was 1 complete response of 14 months duration and 6 partial responses. Among those patients not previously irradiated, the response rate was 57% (4/7). Among the radiated patients, the response rate was 30% (3/10) with all responses occurring in the radiation field. CONCLUSION: This combination of cis-platinum and gemcitabine is a well-tolerated regimen which exhibits high activity in advanced, recurrent, or persistent squamous cell cervical cancer.     

Cis-platinum, vincristine and peplomycin (CVP) therapy for carcinoma of the uterine cervix

Surgery and radiation therapy are major treatments for carcinoma of the uterine cervix. However, there has been little improvement in survival recently. Since 1982, we have introduced multiagent chemotherapy consisting of cis-platinum, vincristine and peplomycin (CVP) to control systemic disease and to do cytoreduction prior to operation and/or radiation therapy. Our results are as follows. Thirty-one patients have been treated with CVP. Among eleven patients initially treated with CVP, 7 patients responded well to this regimen alone, including three patients who entered complete clinical remission. This indicates that this regimen is effective against carcinoma of the uterine cervix. Two patients who were thought to be candidates for radical hysterectomy became able to have less extensive surgery following CVP treatment. It is difficult for this CVP combination to control bulky tumors within previously radiated fields, probably because of poor vascularity due to pelvic fibrosis caused by radiation. Metastatic disease were also able to be controlled by this combination especially in two patients with pulmonary metastases. Nausea, vomiting and mild myelosuppression were frequently encountered, but they were tolerated well by the patients. However, great care must be taken in using peplomycin when the cumulative dose becomes large.     

A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer

OBJECTIVE: Cisplatin-based combination therapy produces higher response rates and improved survival, in comparison to single-agent cisplatin in the treatment of cervical cancer. Cisplatin and paclitaxel (PT) requires a prolonged infusion and is less convenient and more toxic than the combination of carboplatin and paclitaxel (CT) leading to more widespread use of CT. The objective of this study was to compare response rate and survival in patients with cervical cancer treated with PT or CT. METHODS: A retrospective search of databases at the University of Oklahoma, Washington University-Barnes Jewish Christian Hospitals, Johns Hopkins University, and University of Alabama at Birmingham identified patients with stage IVB, recurrent or persistent cervical cancer who were treated with PT or CT. RESULTS: A total of 62 patients were identified. 14 were treated with PT and 48 with CT. There were no statistical differences between the groups in terms of demographics, prior radiation therapy, or median number of cycles. There was a trend toward a larger number of patients in the CT arm having received prior cisplatin/radiation (p=0.07). Objective responses occurred in 29% of patients receiving PT vs. 53% of patients receiving CT. With a median follow-up of 9 months, survival was not different with a median survival of 14 and 11 months, respectively. CONCLUSIONS: In this retrospective evaluation, CT compares favorably with PT and demonstrates a superior overall response rate. Because of its ease of administration and improved toxicity profile, CT should be considered in the treatment of advanced, recurrent or progressive cervical cancer.     

Pemetrexed (Alimta®, LY231514) demonstrates clinical activity in chemonaive patients with cervical cancer in a phase II single-agent trial

The objective of this study was to determine the response rate in chemonaive patients with inoperable, locally advanced, recurrent, or metastatic cervical cancer treated with pemetrexed (Alimta, LY231514), a multitargeted antifolate. The patients were treated with either 500 mg/m(2) (11 patients) or 600 mg/m(2) (24 patients) of pemetrexed, administered as a 10-min infusion on day 1 of a 21-day cycle. Patients receiving 500 mg/m(2) dose also received 5 mg/day oral folic acid supplementation beginning 2 days prior and ending on day 3 of each cycle. Of the 34 patients evaluable for efficacy, six patients (18%) had partial response, with median response duration of 3.8 months (range, 3.3-6.6 months). Twenty-four patients (71%) had stable disease, one patient (3%) had progressive disease, and three patients could not be assessed. Median overall survival was 15.2 months (range, 2.9-35.3+ months). Grade 4 hematologic toxicities consisted of neutropenia (37%), leukopenia (9%), anemia (6%), and thrombocytopenia (3%). One patient died of hypotensive shock associated with frank rectal hemorrhage that was considered to be related to the study drug. We conclude that pemetrexed therapy showed moderate activity, similar to other active agents, in the treatment of locally advanced or metastatic cervical cancer.     

Cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria: therapeutic implications

This study was designed to determine whether the presence of progesterone receptors (PR) and/or estradiol receptors (ER) could be used to predict progestin responsiveness of recurrent or advanced endometrial cancers. We have demonstrated the presence of physicochemically similar cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria. All normal endometria contained both PR and ER. Seventy-three percent of endometrial hyperplasias were PR(+) and 93% were ER(+). A decreasing concentration of progesterone receptor activity was observed with increasing tumor anaplasia [grade 1, 84% PR(+); grade 2, 55% PR(+); grade 3, 22% PR(+)] and in irradiated tumors. A statistically significant (p less than 0.001) relationship has been demonstrated between the presence of specific cytoplasmic PR and response to progestin therapy in recurrent or advanced endometrial adenocarcinomas. Thus, we conclude that a PR assay may be used to help select the most appropriate therapy for patients with recurrent or advanced endometrial adenocarcinoma.     

Phase II study of topotecan and paclitaxel for recurrent, persistent, or metastatic cervical carcinoma

OBJECTIVE: This trial investigated the safety and efficacy of paclitaxel and topotecan combination chemotherapy for patients with advanced cervical cancer (ACC). METHODS: Patients with recurrent, persistent, or metastatic ACC and an ECOG performance status < or =2 were treated with 175 mg/m(2) paclitaxel on Day 1 and 1 mg/m(2) topotecan on Days 1-5 of a 21-day cycle with G-CSF support and the standard pretreatment regimen for paclitaxel. Patients were treated until disease progression or unacceptable toxicity. RESULTS: Fifteen patients were enrolled, and 86 cycles of therapy (median, 5; range, 1-14) were administered. Grade 3/4 toxicities included anemia (47%), leukopenia (27%), neurotoxicity (13%), thrombocytopenia (13%), and diarrhea (13%). Among 13 evaluable patients, 7 (54%) responded (1 complete and 6 partial; 95% confidence interval = 29.2%, 76.8%). Three (23%) patients experienced stable disease. Progression-free and overall survival were 3.77 and 8.62 months, respectively. CONCLUSION: The combination of paclitaxel/topotecan was generally well tolerated and active in the relapsed, recurrent, or metastatic ACC setting, with response rates comparable with those of other current ACC systemic therapies.     

A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study

In this study, 331 patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to control with surgery or radiotherapy were randomized to receive cisplatin 50 mg/m2 as either a continuous infusion over 24 hr or a more rapid infusion at a rate of 1 mg/min. Antiemetic therapy was standardized for the initial course of both regimens as metoclopramide 60 mg at the time of and at 3 and 6 hours after initiation of cisplatin. The overall frequency of objective regression of disease was 18%; the response rate in each regimen was essentially identical. The continuous infusion regimen was associated with a significantly greater percentage of patients who experienced no nausea and vomiting (34% versus 18%, P = 0.002). Other adverse effects included nephrotoxicity, peripheral neuropathy, myelosuppression, and ototoxicity. Both the frequency and severity of these were essentially the same for each regimen.     

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.