OBJECTIVE: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. MATERIALS AND METHODS: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m, days 1 to 4, and intravenous paclitaxel, 175 mg/m, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. RESULTS: Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0-7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5-26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. CONCLUSIONS: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.
OBJECTIVE: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. MATERIALS AND METHODS:Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m, days 1 to 4, and intravenous paclitaxel, 175 mg/m, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. RESULTS: Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0-7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5-26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. CONCLUSIONS: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.
Authors: R S DiPaola; M M Rafi; V Vyas; D Toppmeyer; E Rubin; J Patel; S Goodin; M Medina; P Medina; R Zamek; C Zhang; E White; E Gupta; W N Hait Journal: J Clin Oncol Date: 1999-07 Impact factor: 44.544
Authors: E Kastritis; A Bamias; E Efstathiou; D Gika; G Bozas; P Zorzou; K Sarris; C Papadimitriou; M A Dimopoulos Journal: Gynecol Oncol Date: 2005-07-26 Impact factor: 5.482
Authors: Krishnansu S Tewari; Michael W Sill; Harry J Long; Richard T Penson; Helen Huang; Lois M Ramondetta; Lisa M Landrum; Ana Oaknin; Thomas J Reid; Mario M Leitao; Helen E Michael; Bradley J Monk Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: G R Weiss; P Y Liu; D S Alberts; Y M Peng; E Fisher; M J Xu; S A Scudder; L H Baker; D F Moore; S M Lippman Journal: Gynecol Oncol Date: 1998-12 Impact factor: 5.482
Authors: E A Eisenhauer; P Therasse; J Bogaerts; L H Schwartz; D Sargent; R Ford; J Dancey; S Arbuck; S Gwyther; M Mooney; L Rubinstein; L Shankar; L Dodd; R Kaplan; D Lacombe; J Verweij Journal: Eur J Cancer Date: 2009-01 Impact factor: 9.162
Authors: Bradley J Monk; Michael W Sill; D Scott McMeekin; David E Cohn; Lois M Ramondetta; Cecelia H Boardman; Jo Benda; David Cella Journal: J Clin Oncol Date: 2009-08-31 Impact factor: 44.544
Authors: Vladimir N Anisimov; Irina G Popovich; Mark A Zabezhinski; Maria N Yurova; Margarita L Tyndyk; Ivan V Anikin; Peter A Egormin; Irina A Baldueva; Elena I Fedoros; Sergey E Pigarev; Andrey V Panchenko Journal: Aging (Albany NY) Date: 2016-08-28 Impact factor: 5.682