Quality of life outcomes from a randomized phase III trial of cisplatin with or without topotecan in advanced carcinoma of the cervix: a Gynecologic Oncology Group Study.
ABSTRACT To prospectively assess the impact of treatment with cisplatin alone or in combination with topotecan (CT) on quality of life (QOL) in patients with advanced or recurrent cervical cancer, and to explore the prognostic value of baseline QOL scores.
Patients entered on Gynecologic Oncology Group (GOG) Protocol 179 were expected to complete QOL assessments at four time points using Functional Assessment of Cancer Therapy-General (FACT-G), Cervix subscale (Cx subscale), FACT/GOG-Neurotoxicity subscale (NTX subscale), Brief Pain Inventory (BPI), and UNISCALE (UNI). Adjusting for patient age, baseline scores, and effects of time, we longitudinally examined treatment effect on QOL during and after chemotherapy.
Among patients randomly allocated to receive cisplatin (n = 146) or CT (n = 147), there were no statistically significant differences in QOL up to 9 months after randomization despite more hematologic toxicity in the combination arm. QOL assessments were completed at rates of 98%, 85%, 68%, and 59%, respectively, for the four time points, with similar rates and reasons for nonparticipation between regimens. Baseline FACT-G (P = .0016) and BPI (P = .0001) scores were significantly associated with patient age; older patients had better QOL and less pain. Baseline UNI was positively correlated with FACT-G (r = 0.66; P < .001) and Cx subscale (r = 0.29; P < .001), and negatively related to BPI (r = -0.41; P < .0001). Baseline FACT-Cx (FACT-G + Cx subscale) was associated with survival.
Despite increased toxicity, CT did not significantly reduce patient QOL when compared with cisplatin alone. Patient-reported QOL measures may be an important prognostic tool in advanced cervix cancer.
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ABSTRACT: Increasing resistance to cisplatin as well as the severity of the adverse effects limit the use of this drug, particularly at high doses. Evidence has implicated the importance of autophagy in cancer resistance as well as the fact that various chemotherapy agents induce autophagy in cancer cells. We therefore aimed to first assess the role of autophagy in cisplatin treatment and second to assess whether a nontoxic concentration of cisplatin, together with autophagy inhibition, is able to maintain its cancer-specific cytotoxic action. Three human cervical cell lines were used: a noncancerous ectocervical epithelial cell line (Ect1/E6E7) and 2 cancerous cervical cell lines (HeLa and CaSki). Autophagy was monitored through the presence of the classical protein markers LC-3 II and p62 under basal and treatment conditions, and inhibited using bafilomycin and autophagy protein 5 (ATG5) siRNA under treatment conditions. Cell death was analyzed through examination of the apoptotic markers PARP and caspase-3 through Western blotting, as well as the Caspase-Glo assay to confirm caspase-3/7 activity. Cervical biopsies were analyzed for the presence of LC-3 using Western blotting and immunofluorescence to determine if a correlation between autophagic levels and the progression of the disease exists. Cervical cancer cells exhibit increased basal autophagic levels in comparison to the noncancerous counterparts. Cisplatin treatment enhanced autophagic activity in all 3 cell lines. Inhibition of this autophagic response together with cisplatin treatment leads to significant increases in cancer cell death. Expression profiles of LC-3 in normal, premalignant (low-grade and high-grade squamous intraepithelial lesion), and cancerous cervical tissue revealed that autophagy is significantly up-regulated in HSILs and carcinoma cervical tissue, which emphasized the role of autophagy in the progression of the disease. The inhibition of autophagy improves the cytotoxicity of a nontoxic concentration of cisplatin and provides a promising new avenue for the future treatment of cervical cancer.
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ABSTRACT: Purpose To estimate the antitumor activity of pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, this study will determine the effects of this regimen on progression-free survival and overall survival. Patients and Methods Eligible, consenting patients received pemetrexed 500 mg/m(2) and cisplatin 50 mg/m(2) intravenously repeated every 21 days until disease progression or adverse events prohibited further therapy. Patients received no prior therapeutic chemotherapy, except when administered concurrently with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with Common Terminology Criteria for Adverse Events v 3.0. The primary measure of efficacy was tumor response according to Response Evaluation Criteria in Solid Tumors. The study was stratified by prior radiation therapy. Results From September 2008 to November 2011, 55 patients were enrolled by five Gynecologic Oncology Group member institutions; of those, 54 patients were eligible and assessable. The regimen was well tolerated with 26% receiving more than nine cycles. The most common greater than grade 2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial). The median progression-free survival was 5.7 months, and overall survival was 12.3 months. Conclusion Pemetrexed in combination with cisplatin demonstrates activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix. (C) 2014 by American Society of Clinical OncologyJournal of Clinical Oncology 09/2014; 32(25):2744. DOI:10.1200/JCO.2013.54.7448 · 17.88 Impact Factor
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ABSTRACT: Objective A large proportion of cervical cancer patients have a lower socioeconomic background with inherent barriers to clinical trial participation. We hypothesized that patients participating in a clinical trial would have better outcomes compared to those not enrolled in a trial. Our objective was to review the clinical outcomes of women with recurrent cervical cancer treated on a clinical trial versus those treated off trial. Methods This was a retrospective cohort study of women treated for recurrent cervical cancer on versus off clinical trial between 1998 and 2010. Women participating in Gynecologic Oncology Group clinical trials for recurrent cervical cancer were identified and matched 1:1 with women treated off trial based on age within 10 years, ethnicity, stage at initial diagnosis, histology, primary treatment, and baseline renal function. Results Sixty women with recurrent cervical cancer were identified. Thirty were treated for their recurrence on a clinical trial and were matched to 30 treated off trial. The median number of salvage regimens was 1.0 for the trial group (range 1-5) and 1.5 for the non-trial group (range 1-5) (p=0.74). There was no significant difference in the number of cycles of chemotherapy completed on versus off trial (7.5 vs. 5.9, p=0.44). There was also no significant difference in progression free and overall survival from time of recurrence (4.2 vs. 3.1 months, p= 0.75 and 15.0 vs. 13.8 months, p=0.64) on trial and off trial respectively. Conclusion We found that the progression free and overall survival between women treated with chemotherapy on or off trial for cervical cancer survival is similar.01/2014; DOI:10.1016/j.cogc.2014.06.004