Bleomycin, ifosfamide and cis-platin chemotherapy in recurrent and persistent cervical cancer, a prospective study

Thirty patients with histologically proven recurrent or persistent squamous cell cervical carcinoma were treated with chemotherapy, consisting of a combination of bleomycin, ifosfamide and cis-platin (BIP). All patients were evaluable for response. An objective response was seen in nine of the 30 patients (30%): complete in two (6.7%) and partial in the other seven (23.3%). A total of 39 tumor sites was treated: five responses were observed in 26 irradiated areas (19%), whereas seven responses were observed in 13 nonirradiated areas (53.8%). Side-effects were mainly nausea, vomiting, alopecia, myelosupression, fever and impaired renal function. Encephalopathy was recorded in four patients (severe in one). No patient died from the toxic effects of chemotherapy. The results indicate that BIP is an active combination in recurrent and advanced cervical carcinoma, with acceptable toxicity; however, this combination failed to prove any superiority over other single or multi-drug treatments proposed in the last decade.     

Single agent versus combination chemotherapy in recurrent cervical cancer

OBJECTIVE: Cisplatin and ifosfamide are two most active agents in patients with recurrent and metastatic cervical cancer. Combination of bleomycin, ifosfamide and cisplatinum (BIP) was compared with cisplatinum alone. PATIENTS AND METHODS: One hundred and six patients with recurrent/persistent and metastatic cervical cancer received either a combination of bleomycin, ifosfamide and cisplatinum, (Group A, n = 50) or cisplatinum alone (Group B, n = 56) every 3 weeks for up to 6 courses. Ninety-seven patients were evaluable and were analysed for response and survival. RESULTS: Patients receiving BIP (Group A) had a higher response rate (complete and partial responses), 52.2% vs 29.4%, p < 0.01 with overall median survival, 8 months (1 to 92+ months) vs 6 months (1 to 40+ months), p = 0.18. Chemotherapy responders had a significantly higher survival in both groups compared to the non-responders (Group A: 17 vs 6 months, p < 0.001, Group B: 20.5 months vs 5 months, p < 0.001). Patients in good performance status (ECOG, 0-2) had a significantly higher response rate to chemotherapy (Group A: 70.3% vs 26.3%, p < 0.01, Group B: 38.2% vs 11.7%, p < 0.05). In Group A, patients with extrapelvic disease responded better compared to pelvic disease (83.3% vs 34.5%, p < 0.01). Chemotherapy side effects were mainly nausea/vomiting, alopecia, myelosuppression, reversible encephalopathy (in Group A), and impaired renal functions. Chemotherapy toxicity was higher for patients receiving BIP, 2 patients died of BIP toxicity. Currently, in 'Group A' 8 patients are alive, 7 disease-free and one with disease at a median interval of 51 months after chemotherapy treatment. While in Group B, 3 patients are alive, 2 disease-free and one with disease. CONCLUSIONS: Bleomycin, ifosfamide and cisplatin improved the response rate in recurrent and metastatic cervical cancer compared with cisplatinum alone. However, the toxicity was moderate and survival was not significantly improved. These results need to be confirmed in a phase III, randomized study in larger number of patients.     

A phase II study of ifosfamide and bleomycin in advanced or recurrent cervical carcinoma

Thirty-seven patients with advanced or recurrent cervical squamous cell carcinoma were treated with ifosfamide 1.5 g m⁻² on days 1–5 (with mesna as a uroprotector), and bleomycin 30 mg on day 1, every 3 weeks. A partial response rate of 21% (95%CI: 6–36%) was obtained in patients who had not received prior chemotherapy, with a median duration of response of 5 months. No complete responses were seen. The median survival of all patients was 6 months. Nausea and vomiting, white cell suppression and encephalopathy were the main toxic effects. The results suggest that the addition of bleomycin to ifosfamide is not advantageous and increases toxicity, and that the interaction between these two agents is not contributory to the activity of the bleomycin, ifosfamide and cisplatin combination regimen (BIP). The potentially more severe toxicity of combination regimens must be considered when treating this group of patients.     

Cervical carcinoma: a drug-responsive tumor--experience with combined cisplatin, vinblastine, and bleomycin therapy

Thirty-five patients with advanced cervical cancer were treated with a combination chemotherapy regimen comprising cisplatin, vinblastine, and bleomycin (PVB). Sixty-six percent of 33 evaluable patients showed objective tumor response and complete remissions were seen in six (18%) patients. The median duration of tumor response in patients with recurrent cervical cancer was 24 weeks (range 8 to 104 weeks). Multivariate analysis of pretreatment variables including prior radiotherapy did not identify patients with a higher response probability. Nausea and vomiting were usual side effects of chemotherapy and there was one definite treatment-related death. Cervical cancer is responsive to cisplatin based combination chemotherapy. The role of chemotherapy in conjunction with radiotherapy or surgery in the treatment of locally advanced cervical cancer remains to be defined.     

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.     

Phase II study of tirapazamine plus cisplatin in patients with advanced or recurrent cervical cancer

The aim of this study was to evaluate the activity and toxicity of a tirapazamine (TPZ)/cisplatin drug combination in patients with stage IV or recurrent cervical cancer. The chemotherapy was administered for a maximum of eight cycles every 21 days. TPZ was administered intravenously at 330 mg/m(2) over a 2-h infusion, followed 1 h later by cisplatin intravenously at 75 mg/m(2) over 1 h on day 1. All patients received antiemetics including dexamethasone, ondansetron, and lorazepam. Subsequent doses were unchanged, reduced, or omitted according to observed toxicity and protocol guidelines. Response evaluation was performed every two cycles. Thirty-six patients with stage IV or recurrent cervical cancer were treated. Ninety-four percent of patients had prior radiotherapy. Two patients had prior chemotherapy. There were two complete responses and eight partial responses (27.8%). An additional 11 patients (30.6%) had stable disease as their best response. Response rate was greater in tumors outside of the previously radiated field (44.4% vs 11.1%). The median time to progression was 32.7 weeks. The most frequent grade 3 or 4 adverse events were nausea, vomiting, and fatigue, which occurred in 30.6%, 25%, and 22% of subjects, respectively. Anemia was the most frequent grade 3 or 4 hematologic toxicity at 8.3%. We conclude that the combination of cisplatin and TPZ was reasonably well tolerated in patients with recurrent or advanced cervical cancer. Further evaluation of this drug combination may be warranted.     

Cervical adenocarcinoma, a novel combination chemotherapy with mitomycin C, etoposide, and cisplatin for advanced or recurrent disease.

We review the cases of 31 patients with stage IVb or recurrent cervical adenocarcinoma who were treated with combination chemotherapy utilizing mitomycin C, etoposide, and cisplatin (MEP). The total response rate was 16.1% (95% confidence intervals (CIs), 5. 5 to 33.7%) with 4 patients having a complete response (CR) and 1 having a partial response. In patients with no prior chemotherapy, the response rate was 26.7% (95% CIs, 7.8 to 55.1%) with 2 of these CR patients surviving over 3 years, 1 a disease-free survival. A marked response was found in distant recurrent lesions. The major toxicity was myelosuppression. Forty-five percent of patients had leukocytopenia above grade 3; thrombocytopenia and anemia were not common. In patients with cervical adenocarcinoma and no prior chemotherapy, there was a moderate response to MEP therapy.     

Bleomycin, vincristine, and mitomycin C (BOM) as second-line treatment after failure of cis-platinum-based combination chemotherapy for recurrent cervical cancer.

Seventeen patients with recurrent cervical cancer were prospectively treated with a combination of bleomycin, vincristine, and mitomycin C (BOM). All patients had previously failed a cis-platinum-containing combination regimen. There were no complete responses. Four patients had partial responses, six patients had stable disease, and seven patients had no response. The median length of survival for responders was the same as that for nonresponders (5 months). More than 50% of patients experienced significant toxicity. The combination of bleomycin, vincristine, and mitomycin C appears to be ineffective as a second-line chemotherapy regimen against recurrent cervical cancer previously treated with cis-platinum.     

Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer

OBJECTIVE: To report the utility of the monoclonal, anti-vascular endothelial growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for women with recurrent cervical cancer. METHODS: A retrospective analysis of women with recurrent cervical cancer treated with bevacizumab combination therapy was performed. RESULTS: Six patients were identified. The patients had a median of 3 prior regimens. All of the patients had multisite, metastatic disease. The combination regimen included IV 5-fluorouracil in 5 (83%) patients and capecitabine in one (17%) subject. Treatment was well tolerated. Grade 4 toxicity occurred in one patient who developed neutropenic sepsis. Clinical benefit (CR, PR, or SD) was noted in 67% of the subjects. This included 1 (17%) complete response, 1 (17%) partial response and two (33%) patients with stable disease. The median time to progression for the four women who demonstrated clinical benefit was 4.3 months. CONCLUSIONS: Combination bevacizumab is well tolerated and displayed encouraging anti-tumor activity in heavily pretreated recurrent cervical cancer.     

Phase I/II dose finding study of combination cisplatin and gemcitabine in patients with recurrent cervix cancer

OBJECTIVES: To evaluate the toxicity and efficacy of cisplatin and gemcitabine in women with recurrent cervical cancer. METHODS: A multi-institutional phase I/II dose finding study of cisplatin and gemcitabine delivered to women with recurrent previously radiated cervical carcinoma. RESULTS: Twenty eight patients were enrolled. The mean and median age of patients was 51 years (age range 35 to 70 years). Chemotherapy was given on a 28-day cycle; cisplatin was administered at a fixed dose of 50 mg/m(2), day 1 and gemcitabine, days 1, 8, and 15. Gemcitabine doses started at 600 mg/m(2) (dose level 1) and were escalated by 100 mg/m(2)/dose level until 1000 mg/m(2) (dose level 5). Twenty seven patients were evaluable for toxicity and disease response, and 75 cycles of chemotherapy were administered. Toxicities were predominantly hematological; 18% of patients experienced grade 3 anemia, 37% grade 3 and 11% grade 4 leukopenia, 41% grade 3 neutropenia, and 26% grade 3 thrombocytopenia. The maximally tolerated dose (MTD) was not reached. One patient experienced a dose-limiting toxicity on dose level 2 (febrile neutropenia). One patient had a CR and 3 patients had a PR to therapy (15% response rate), 41% of patients had SD, and 44% had progression of cancer. Median survival was 11.9 months. CONCLUSION: Although this 28-day gemcitabine and cisplatin regimen in recurrent cervix cancer has tolerable toxicity, 21-day regimens are recommended because of improved practicality, higher dose intensity, and higher response rates.     

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 vindesine in disseminated squamous cell carcinoma of the uterine cervix: an EORTC Gynecological cancer Cooperative Group study

Abstract. Vermorken JB, Landoni F, Pecorelli S, Piccart MJ, van derBurg MEL, ten Bokkel Huinink WW, George M, Greggi S, Rotmensz N. Phase II study of vindesine in disseminated squamous cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Int J Gynecol Cancer 1991; 1 : 248–252.
Twenty-nine patients with disseminated squamous cell carcinoma of the uterine cervix were treated with a 3 mg/m² weekly i.v. bolus schedule of vindesine for 6 weeks (thereafter every 2 weeks). Twenty-seven patients were evaluable for response, 19 of whom had received prior chemotherapy (14 also vincristine). Five of the 27 patients (19%) showed a partial response, all being part of the 22 patients with only distant metastases. No objective response were observed among five patients who also had loco-regional recurrent disease. The median duration of response was 21 (11–58) weeks. Dose-limiting toxic effects were leukopenia and peripheral neuropathy. Vindesine warrants further study in combination chemotherapy protocols for cervical cancer.     

Chemotherapy for recurrent, metastatic, or persistent cervical cancer: a systematic review

To determine the front-line chemotherapeutic options for women with recurrent, metastatic, or persistent cervical cancer. The Medline, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing chemotherapy regimens for patients with recurrent, metastatic, or persistent cervical cancer. Studies were included if response rate, survival, toxicity, or quality of life data were reported. Fifteen RCTs were identified. The proportion of patients with prior chemoradiotherapy ranged from 0% to 57%. Four of the 15 RCTs detected significant improvements in overall response with combination cisplatin-based chemotherapy when compared with single-agent cisplatin. One of the 15 RCTs reported a significant median survival advantage with topotecan and cisplatin when compared with single-agent cisplatin (9.4 vs 6.5 months, P = 0.017); 57% of patients in this trial had previous chemoradiotherapy. Significant increases in grade 3 and 4 adverse events, especially severe hematologic toxicities, were detected among patients treated with that combination of chemotherapy. Thus, we conclude that cisplatin and topotecan should be discussed as a reasonable treatment option for appropriate patients who may wish to maximize the response and survival benefits associated with combination chemotherapy. Patients should understand that prior chemoradiotherapy with cisplatin may moderate the benefits observed, and that the relative benefits in response and survival outcomes come at the expense of increased toxicity. The improvement in median survival of 2.9 months represents a novel survival benefit in this difficult-to-treat patient population. Further randomized trials are needed to inform the role of single-agent or combination chemotherapy regimens, particularly in patients with prior chemoradiotherapy.     

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.     

IAP方案治疗复发及耐药性卵巢上皮性癌的临床分析

目的 探讨奥沙利铂+表柔比星+异环磷酰胺(1AP)方案治疗复发及耐药性卵巢上皮性癌(卵巢癌)的有效性和安全性.方法 2004年7月-2008年1月间,北京大学人民医院共收治复发及耐药性卵巢癌患者25例,均行IAP方案(其中奥沙利铂130 mg/m2,表柔比星50～60 mg/m2,异环磷酰胺3～4 g/m2)化疗,疗程间隔3周.其中接受≥2个疗程IAP方案化疗的21例纳入本研究,并对其疗效及化疗副反应进行回顾性分析.21例患者共接受80个疗程的IAP方案化疗,化疗疗程的中位数为4个[(2～7)个].结果 (1)疗效评价:21例患者中,完全缓解10例(48%),部分缓解5例(24%),病情稳定1例(5%),病情进展5例(24%),有效率达71%.其中,原发性铂类药物耐药患者的有效率为60%(6/10),继发性铂类药物耐药患者的有效率为7/8.IAP方案化疗后肿瘤无进展时间的中位数为11个月(1～33个月),总生存时间的中位数为31个月(1～71个月).(2)副反应:80个疗程的化疗中,血液学副反应(Ⅲ～Ⅳ度)的发生率为30%(24/80),非血液学副反应包括周围神经毒性反应(38%,30/80)、浅表静脉炎(29%,23/80)等.结论 IAP方案用于复发及耐药性卵巢癌患者的三、四线挽救性化疗,其疗效较好,且副反应可耐受,但有待扩大样本进一步验证.     

Topotecan for recurrent cervical cancer after platinum-based therapy

Abstract. Abu-Rustum NR, Lee S, Massad LS. Topotecan for recurrent cervical cancer after platinum-based therapy.
The activity and toxicity of topotecan in women with recurrent cervical cancer are described from a case series of women with recurrent cervical cancer who had measurable disease and were not amenable to cure by surgery or radiation. All patients had prior platinum-based chemotherapy and developed progressive disease. Topotecan was given as 1 mg/m²/day over 30 min for 5 days every 3 weeks until progression of disease or prohibitive toxicity. Between July 1998 and July 1999, 12 patients received a total of 20 cycles of topotecan. Median age was 41 years (range 21–62), and 11 (92%) patients had prior whole pelvic radiation. The mean number of topotecan cycles was 1.5 (median 1, range 1–3). There were two partial responses (16.7%; 95% CI, 2% to 48%), both in prior radiation fields. Five patients required red blood cell transfusions, four had grade II nausea and vomiting, two developed sepsis (one with neutropenia), one developed fever, and one reported hyperpigmentation. There were no treatment-related mortalities. Although topotecan appears to exhibit modest activity in recurrent cervical cancer after radiation and platinum-based therapy, bone marrow toxicity may limit the utility of this regimen without hematopoietic growth factor support.     

Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer

AIM: To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix. METHODS: From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded. RESULTS: The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035). CONCLUSION: Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer.     

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.     

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.     

The impact of age in the outcome of patients with advanced or recurrent cervical cancer after platinum-based chemotherapy

OBJECTIVES: Cervical cancer is a disease of middle-aged and elderly but still there are young women diagnosed with advanced disease that is incurable with local treatment and is treated with platinum-based combination chemotherapy. It is unknown whether these young patients have a poorer outcome compared to older patients or whether elderly patients have inferior outcome than younger patients when treated with combination chemotherapy. METHODS: We compared the outcome between young (<35), elderly (>70) and middle-aged (35-70) women who were treated with platinum-based combination chemotherapy for advanced, recurrent or persistent disease. RESULTS: Two hundred and eighteen patients were included in our database. The baseline clinical and disease characteristics were not different between age groups but anemia and thrombocytosis were more frequent in younger patients. Median survival for all patients was 13.4 (95%CI 11-15.8) months while survival of patients<35 years of age was 9 months (95% CI 5.8-12), of patients older than 70 was 10 months (95% CI 6.9-13) of patients 35 to 70 years of age was 14.5 months (95% CI 11-18) (p=0.004). Multiple factors were significant for survival in univariate analysis but only weight loss, pain score and relapse inside an irradiated filed were significant predictors of outcome in multivariate analysis. CONCLUSIONS: Very young (<35) and elderly (>70) patients have a worse prognosis after treatment with combination chemotherapy for advanced or recurrent cervical cancer. Nevertheless, this difference is not significant when adjusted for other prognostic factors.