Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study

PURPOSE: A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of capecitabine in women with measurable platinum-sensitive ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities. EXPERIMENTAL DESIGN: Patients were treated with a daily starting dose of 2500 mg/m2/day (divided in two doses given every 12 h) for 14 days of each 21-day cycle. Genotyping in the 5' and 3' ends of TS was performed in DNA from 23/23 pre-treatment blood specimens. Relative gene expression of TS, DPD, and TP was quantified in 18/21 paraffin-embedded tumor specimens. RESULTS: Of the 27 patients enrolled on study, 2 were never treated leaving 25 patients evaluable. Two patients (8.0%) achieved a partial response, 13 (52%) exhibited stable disease, 5 (20%) displayed increasing disease, and response could not be assessed in 5 (20%). The median time to progression and survival was 3.9 and 21.2 months, respectively. The most common serious toxicities were nausea/vomiting, gastrointestinal, and dermatological. There was one treatment-related death. TS expression was associated with severe nausea/vomiting (P = 0.039), but not with other severe toxicities. TS genotype or expression of DPD or TP was not associated with any of the severe toxicities. CONCLUSIONS: Based on the low response rate, this trial was closed after the first stage of accrual, the drug was not selected for further study in this patient population, and biomarker associations with response could not be assessed.     

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.     

A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study

OBJECTIVE: The toxicity and activity of intravenous topotecan were assessed in a multicenter Phase II study (GOG 76-U) in patients with advanced, recurrent, or persistent squamous cell carcinoma of the uterine cervix. METHODS: Intravenous topotecan was administered at 1.5 mg/m2 per day for 5 consecutive days every 4 weeks in patients without prior chemotherapy, aside from chemosensitizing agents used in conjunction with radiotherapy. The study required histologic confirmation of primary diagnosis, adequate performance status, and measurable disease to assess response. A two-stage design for accrual was used to allow for early termination of the study should inadequate response or excessive toxicity be an issue. Modifications of dose were based on hematologic toxicity. Treatment was continued until progression of disease was documented or adverse effects prohibited further therapy. RESULTS: A total of 49 patients were entered on study: of these 5 were never treated, and 1 was not evaluable for response. More than 88% (38 of 43 patients) had received prior radiotherapy. A median of two courses were administered per patient with a range of 1 to 14 cycles. Grade 4 neutropenia occurred in 68% and grade 4 thrombocytopenia in 18% of patients. Nonhematologic toxic effects were infrequent and not dose-limiting. The overall response rate (complete and partial) was 18.6%. The median progression-free survival was 2.4 months. CONCLUSIONS: Topotecan administered at this dose and schedule demonstrated moderate activity albeit at a cost of substantial hematologic toxicity in patients with advanced, recurrent, or persistent squamous cell carcinoma of the cervix.     

The outcome of advanced or recurrent non-squamous carcinoma of the uterine cervix after platinum-based combination chemotherapy

BACKGROUND: Data about the outcome and prognostic factors in the group of patients with non-squamous cell advanced or recurrent carcinomas of the uterine cervix are limited. We compared the outcome of patients with non-squamous with that of squamous cell carcinomas after platinum-based combination chemotherapy as first line therapy for stage IV or recurrent cervical carcinoma. PATIENTS AND METHODS: A total of 200 patients with stage IV or recurrent carcinomas of the cervix received platinum-based combination chemotherapy and were included in our analysis. RESULTS: There were 58 patients with non-squamous and 142 patients with squamous cell carcinomas. Response to chemotherapy was 53.5% in non-squamous vs. 43.5% in squamous carcinomas. Histology was not an independent predictor of tumor response (P = 0.797). Response rates were lower in patients with relapse only in a previously irradiated area in both squamous (26.9% vs. 53.5%, P = 0.005) and non-squamous carcinomas (47.1% vs. 65%, P = 0.270). Weight loss was the only significant predictor of survival in non-squamous histology patients (P < 0.0001). There was no significant difference in median survival between squamous (11.57 months [95% CI 9.35-13.79]) and non-squamous carcinomas (19.05 months [95% CI 13.63-24.47]) (P = 0.064). After adjustment for independent prognostic factors (ECOG performance status and weight loss), differences in survival remained not significant. CONCLUSION: Our study showed a similar outcome for both squamous and non-squamous stage IV or recurrent cervical carcinomas treated with platinum-based combination chemotherapy.     

Phase II evaluation of oxaliplatin in previously treated squamous cell carcinoma of the cervix: a gynecologic oncology group study

OBJECTIVE: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with previously treated squamous cell carcinoma of the cervix. METHODS: Eligible patients were to have measurable disease and not more than one prior chemotherapy regimen that could include carboplatin or cisplatin but not oxaliplatin. Oxaliplatin 130 mg/m(2) was administered intravenously over 2 h. This treatment was repeated every 21 days until progression of disease or adverse effects prohibited further therapy. RESULTS: Twenty-eight patients were entered onto this study, of whom 24 were evaluable for toxicity and 22 were evaluable for response; 23/24 evaluable patients had had prior platinum. There were two (8.3%) responses. One patient achieved a complete response which lasted 2.2 months, and a second patient attained a partial response which lasted 3.2 months. Nine (37.5%) patients had stable disease with a median duration of 7.6+ (3.1-21.2) months. The most frequently reported drug-related toxicities consisted of anemia, nausea and vomiting, and neurotoxicity. Three (12.5%) patients had a grade 3 allergic response that was infusion-related and was largely resolved by increasing infusion time. CONCLUSIONS: Oxaliplatin has limited activity in patients with persistent or recurrent squamous cell carcinoma of the cervix at the dose and schedule tested.     

Cisplatin and pentoxifylline in advanced or recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group

OBJECTIVE: The aim of this study was to determine the antitumor activity and toxicity of cisplatin and pentoxifylline in previously treated patients with squamous cell carcinoma of the cervix. METHODS: A Gynecologic Oncology Group (GOG) Phase II trial of recurrent squamous cell cervical cancer using standard GOG response and toxicity criteria was performed. RESULTS: A total of 47 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered. The starting dose was 75 mg/m(2) of cisplatin every 21 days and 1600 mg of pentoxifylline PO every 8 h for nine doses during each course. Forty patients were evaluable for response and 44 were evaluable for toxicity. Of the 40 evaluable patients, 37 had received prior radiotherapy and 35 had received prior chemotherapy. A median of three courses were given (range: 1-7). Among evaluable patients, 1 had a complete response (2.5%) and 3 had a partial response (7.5%) for an overall objective response rate of 10%. The complete responder had not previously had chemotherapy. Grade 3 or 4 toxicity was predominantly nausea and vomiting (32%) and hematologic toxicity (23%). CONCLUSIONS: The combination of cisplatin and pentoxifylline at the dose and schedule tested has limited activity in previously treated advanced or recurrent cervical cancer.     

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.     

Prolonged oral etoposide in recurrent or advanced non-squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study

OBJECTIVE: Previous studies by the Gynecologic Oncology Group have demonstrated a 7% response rate with bolus etoposide as second-line therapy in nonsquamous cell carcinoma of the cervix. Prolonged oral etoposide, which exploits the schedule dependency of this agent, has demonstrated increased activity in squamous carcinoma of the cervix compared with bolus administration. To evaluate prolonged oral etoposide in nonsquamous cell carcinoma of the cervix, the current phase II trial was conducted. METHODS: Eligibility included nonsquamous cell cancer of the cervix, measurable disease, no more than one prior chemotherapy regimen no prior etoposide, WBC > or = 3000/microl, platelets > or = 100,000/microl, serum creatinine < or = 2 mg%, and adequate hepatic function. The starting dose was 50 mg/m(2)/day (40 mg/m(2)/day for prior radiotherapy) for 21 days, every 28 days. Based on toxicity, dose escalation to a maximum dose of 60 mg/m(2)/day was prescribed. RESULTS: Fifty-two patients were entered on this study, with 47 evaluable for toxicity and 42 evaluable for response. A median of three (range: 1-12) courses were given. Thirty-four patients received prior radiation therapy and 15 received prior chemotherapy. Oral etoposide was well tolerated, with grade 4 neutropenia occurring in 29.8% and grade 4 thrombocytopenia occurring in 8.5% of patients. Three complete (7.1%) and two partial (4.8%) responses were observed. All of the responses were seen in chemotherapy-na?ve patients (5/27); four of five had disease in nonirradiated sites. CONCLUSION: Prior radiation therapy significantly limited our ability to deliver prolonged oral etoposide. At this dose, this regimen is moderately active in chemotherapy-na?ve patients with nonsquamous cell carcinoma of the cervix.     

Chemotherapy of squamous cell carcinoma of the cervix

Four cases of recurrent squamous cell carcinoma of the cervix were treated with a combination of bleomycin and mitomycin C. There was a complete tumor response in at least 2 of the patients treated. Response is well documented with an external tumor marker visible on 1 patient.     

Rapid progression of squamous cell carcinoma of the cervix after hyperbaric oxygenation

The role of hyperbaric oxygenation in the treatment of radiation-induced sequelae and chronic ulcer is well established. On the contrary, a possible cancer-causing or growth-enhancing effect by hyperbaric oxygenation was highly controversial. Herein, we present a 55-year-old Chinese woman with recurrent squamous cell carcinoma of the cervix on her left inguinal area. She received concurrent chemoradiation therapy followed by radical inguinal lymphadenectomy due to persistent tumor mass. The patient was complicated with severe radiation fibrosis and unhealed wounds, so she was treated with hyperbaric oxygenation (HBO). However, the patient died of complications of the disease after completing HBO therapy I month later and autopsy of the patient showed carcinomatosis of the abdominal cavity and lower abdominal wall. Because previous studies have been inconclusive regarding the effect of HBO on tumor cells, we reviewed the possible relation between the HBO and tumor cells.     

Post-treatment serial serum squamous cell carcinoma antigen (SCC) in the monitoring of squamous cell carcinoma of the cervix

Serum squamous cell carcinoma antigen (SCC) was raised in 62% of 308 patients with squamous cell carcinoma of the cervix before treatment. Post-treatment SCC levels were raised in 69 patients (22.4%). Retrospective review showed that persistently raised SCC level after treatment was significantly associated with persistent or recurrent disease in squamous cell carcinoma of the cervix. The specificity of persistently raised SCC level in association with recurrent disease was 98.2%. The sensitivity in association with recurrent disease was 74.7%. The positive predictive values was 94.2%. The median lead time for recurrence was 4 months. SCC was raised in 38% of patients with clinical evidence of disease in the vagina. One patient had raised SCC one month prior to clinical detection of vaginal metastasis and was salvaged by an exenterative procedure. SCC was raised in 71–91% of patients with metastatic disease in the lung, lymph nodes or other distant sites. Thus, persistently raised SCC level after treatment of squamous cell carcinoma should alert the clinician to look for recurrent disease especially in distant metastatic sites. Post-treatment raised SCC level was associated with less than 5% 5-year survival rate whereas in patients with normal SCC level, the 5-year survival rate was 87%.     

Chemosensitivity testing with cis-platinum(II) diamminedichloride: I. A new concept in the treatment of carcinoma of the cervix

A relatively simple, clinically applicable approach for determining the in vivo sensitivity of squamous cell carcinoma of the cervix to cis-platinum(II) diamminedichloride (DDP) is described. Histologic and cytologic characteristics in sequential cervical biopsies were employed to evaluate the sensitivity of tumor to platinum therapy. The remarkable similarity in histologic response of squamous cell carcinoma of the cervix when treated by platinum or radiation therapy suggests that this system might help to identify the patient who would most benefit from systemic platinum chemotherapy, just as it has been useful in identifying patients who can benefit from radiation therapy.     

The significance of peritoneal cytology in patients with carcinoma of the cervix

Between 1972 and 1977, 141 patients with benign gynecologic disease and 149 patients with carcinoma of the cervix were evaluated with peritoneal fluid cytology at time of celiotomy. There was no positive cytology (malignant cells) in the benign disease group. The overall incidence of positive peritoneal cytology in the cervical group was 8.1%. Positive peritoneal cytology was found four times more frequently in adenocarcinoma and adenosquamous carcinomas than squamous carcinomas. The incidence in patients undergoing surgery for recurrent or persistent carcinoma after radiation therapy was 22.6% compared to 4.5% in those treated primarily with definitive surgery. The prognoses do not seem to be influenced by peritoneal cytology status when other poor prognostic factors were considered.     

Phase II trial of capecitabine in recurrent squamous cell carcinoma of the cervix

PURPOSE: To determine the efficacy and safety of capecitabine in women with inoperable, recurrent, or metastatic squamous cell cervical cancer. PATIENTS AND METHODS: In a phase II IRB approved trial, capecitabine was given at a dosage of 2000 mg/m2/day orally in a divided dose daily for 14 days followed by a 7-day rest period. A standard dose modification scheme was used with one allowed dose reduction or dose escalation. National Cancer Institute criteria for progression, response, and toxicity were utilized. Quality of life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy, which included a subscale for cervical cancer. RESULTS: Twenty of 23 enrolled patients were evaluable for response. Stable disease was noted in 5 patients, with a median duration of response of 3.5 months (range, 3-6.5 months). No partial or complete responses were seen. Common grade 3 toxicities were fatigue (30.4%); abdominal pain, constipation, hand-foot syndrome, nausea, and vomiting (8.7% each); as well as dyspnea, headache, and coagulopathy (4.3% each). There were no grade 4 toxicities. All patients with previous exposure to infused 5-FU had evidence of progression. No statistically significant changes in quality of life were noted from baseline to post-cycle 2. CONCLUSION: Single-agent capecitabine in patients with recurrent cervical cancer resulted in no objective responses. Although capecitabine is a well-tolerated regimen, as a single agent, it offers minimal benefit in a poor-prognosis cervical cancer population.     

IGF-1R expression in localized cervical carcinoma patients treated by radiochemotherapy

PURPOSE: To assess the expression of IGF-1R in cervix carcinoma patients treated by radiotherapy and concomitant chemotherapy, its relation to clinical and pathologic prognostic factors and its role in predicting clinical outcome. MATERIALS AND METHODS: Sixty consecutive patients suffering from localized cervix carcinoma were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in March 2006. Patients were staged following the TNM classification. All patients were referred to pelvic radiation up to doses of 45-64.80 Gy in 1.8-2 Gy fractions followed brachytherapy treatment. External radiotherapy boost was used in one patient not receiving brachytherapy (total dose up to 64.80 Gy). All patients received concomitant cisplatin at 40 mg/m(2)/week doses during pelvic radiation. IGF-1R expression was studied by immunohistochemistry in paraffin-embedded tumor tissue. RESULTS: IGF-1R was expressed in 56 patients (93.7%) and no relation was found with clinicopathological variables. Complete response after treatment was observed in 50 patients (83.3%). Clinical stage of the disease and clinical response to radiotherapy were the most important prognostic factors related to survival. Low (negative and fairly) IGF-1R tumor expression was correlated to better long-term Local and Regional Disease Free Survival (p=0.045), Disease-Free Survival (p=0.045), Cause-Specific Survival (p=0.032) and Overall Survival (p=0.021) in patients achieving a complete response. CONCLUSION: High IGF-1R expression is related with reduced long-term local control due to tumor disease radiochemoresistance in patients who initially respond to definitive radiotherapy and concomitant chemotherapy.     

Active intralymphatic immunotherapy of uterine cervical carcinoma with viral oncolysate: a pilot study

A pilot clinical trial was conducted in patients with squamous carcinoma of the uterine cervix to evaluate the clinical and biologic effects of active intralymphatic immunotherapy (AILI) with allogenic viral oncolysate (VO) prior to radiation therapy. Sixteen patients with advanced primary squamous carcinoma of the uterine cervix and lymph node metastases underwent bipedal intralymphatic injections of VO. VO was derived from lysates of cervical carcinoma cells that had been infected with influenza A virus. AILI was repeated after 2 weeks and followed one week later by standard or extended-field radiation therapy (RT). The first seven patients were treated at one of the three dose levels: 6 mg (three patients), 12 mg (three patients) and 18 mg (one patient). Remaining patients were treated at the 12 mg dose level. Sixteen patients received 63 injections (one patient received three of four doses) of AILI-VO without significant toxicity. Eleven patients have died of persistent or recurrent carcinoma with a total median survival of 19.4 months. Examination of humoral and cellular immunity during AILI-VO showed an increase in the serum liters of antibodies to a surface antigen on cervical carcinoma cells and to the influenza virus. Increased non-MHC restricted lymphocyte cytotoxicity was exhibited by three of four patients treated above the first dose level. Two of the three patients are survivors. By contrast, lymphocytes of patients treated with AILI-VO exhibited either an increase or a decrease in proliferation responses to cervical carcinoma cells. Similarly, post-treatment lymphocytes exhibited either helper or suppressor inducer effects on pre-treatment lymphocytes.     

Phase II trial of topotecan and cisplatin in persistent or recurrent squamous and nonsquamous carcinomas of the cervix

OBJECTIVE: Cisplatin is a standard treatment in advanced, recurrent cervical cancer. Because topotecan is an established treatment in gynecologic malignancies such as ovarian cancer and exhibits nonoverlapping toxicity with cisplatin, a phase II trial was conducted to evaluate the tolerability and antitumor activity of a cisplatin/topotecan doublet in persistent or recurrent cervical cancer patients. METHODS: Patients with bidimensionally measurable persistent or recurrent squamous cell and non squamous cell cervical cancer and adequate bone marrow were enrolled. Patients received 50 mg/m(2) of cisplatin intravenously over 1 h on Day 1 and 0.75 mg/m(2) of topotecan intravenously over 30 min on Days 1, 2, and 3 of 21-day cycles for six cycles or until disease progression. Tumor response and regimen toxicity were assessed using established Gynecologic Oncology Group criteria. RESULTS: Thirty-two of 35 enrolled patients were evaluable for toxicity and tumor response. All but 2 evaluable patients had received previous radiotherapy. No patient received prior chemotherapy. The cisplatin/topotecan doublet was well tolerated, with 77 and 78% of courses given without interruption or delay and at full doses, respectively. As anticipated, the most common toxicity was hematologic, with grade 3/4 neutropenia and thrombocytopenia reported in 30 and 10% of cycles, respectively. The overall response rate was 28% (9/32), with 3 complete and 6 partial responses. The antitumor response in nonirradiated fields (30%) was similar to the response observed in previously irradiated fields (33%), suggesting good drug penetration. Median duration of response was 5 months (range, 2 to 15+ months). An additional 9 (28%) patients achieved stable disease. Median survival was 10 months, with 3 patients in lasting remission. CONCLUSIONS: These results demonstrate that the cisplatin/topotecan combination is safe, well tolerated, and active in persistent or recurrent cervical cancer patients. A phase III, multicenter trial is under way (cisplatin/topotecan versus cisplatin) based on these favorable results to confirm the safety and efficacy profile in this patient population.     

Evaluation of bolus cis-platinum and continuous 5-fluorouracil infusion for metastatic and recurrent squamous cell carcinoma of the cervix

The combination of cis-platinum and 5-fluorouracil has been reported to act synergistically with improved response rates in squamous cell carcinomas of the head and neck. The activity of bolus cis-platinum and continuous infusion of 5-fluorouracil in 24 patients with recurrent and metastatic squamous cell carcinoma of the cervix was evaluated. Twelve patients were stage I, 3 were stage II, 5 were stage III, and 4 were stage IV cervical carcinomas. Among the 24 patients, there were 4 complete and 8 partial responses (50%). The overall median response was 24 weeks. The overall cumulative survival was 55% at 40 weeks and 40% at 1 year after beginning this regimen. Complications included 4 patients who developed leukopenia, 3 thrombocytopenia, 11 stomatitis, 14 nephrotoxicity, 4 peripheral neuropathy, and 6 ototoxicity. The combination of cis-platinum and continuous infusion of 5-fluorouracil appears to have useful activity in patients with recurrent or metastatic squamous cell carcinoma of the cervix.     

An extra-adrenal pheochromocytoma mimicking lymph node metastasis from a cervical cancer

A paraaortic nodule was removed during exploration for pelvic exenteration in a patient with persistent squamous cell carcinoma of the cervix. On frozen section the excised tissue was interpreted as metastatic tumor. Subsequent permanent sections and electron microscopy confirmed the nodule to be a paraganglioma. The coexistence of a paraganglioma and recurrent squamous cell carcinoma created an interesting management problem in terms of prognosis and further therapy.     

A Phase II Trial of CPT-11 in Recurrent Squamous Carcinoma of the Cervix: A Gynecologic Oncology Group Study

Objective.To determine the response rate and associated toxicity of weekly CPT-11 in squamous carcinoma of the cervix.Methods.From October 1994 to May 1996, the Gynecologic Oncology Group (GOG) conducted a Phase II trial in patients with recurrent squamous cervix carcinoma. The schedule employed weekly ×4 intravenous CPT-11 at 125 mg/m²followed with a 2-week rest, to be repeated until disease progression or unacceptable toxicity. Eligibility criteria were a GOG performance status of 0–2, adequate bone marrow reserve, adequate liver function, and serum creatinine <2 mg%. None of the patients had received prior chemotherapy other than radiation sensitizers. Standard GOG toxicity and response criteria were used.Results.Fifty-four patients were entered into the trial. Three patients were ineligible because of wrong cell type (N= 2) or inadequate pathology material (N= 1). Two were inevaluable because of inadequate trial of drug. An additional 4 patients were inevaluable for response. Thus, 49 were evaluable for toxicity and 45 were evaluable for response. The median age of patients was 45 years (range, 29–71 years). The median number of weekly doses delivered was 7 (range, 1–46). The incidence of grade 4 neutropenia and anemia was 6.1 and 4.1%, respectively. Nineteen patients (38.8%) developed gastrointestinal (GI) toxicity including 8 with grade 3 and 11 with grade 4 severity. The overall response rate was 13.3% (6/45). There was 1 patient death from GI toxicity. There was one complete response of 8.8 months duration and 5 partial responses.Conclusion.This schedule of CPT-11 exhibits modest activity with moderate toxicity in patients with recurrent squamous carcinoma of the cervix.