Nine potentially relevant studies were identified and assessed independently by both reviewers. One of the citations compared IP chemotherapy with no further treatment (10), but the types of participants (ovarian cancer patients with a pathologically complete remission after platinum-based IV chemotherapy) did not fit this review's eligibility criteria. Sensitivity analysis was applied to determine if exclusion of this trial would affect the results of the meta-analysis. Data from all randomized patients from the remaining eight trials were made available, and so the main results for this comparison are based on 1,819 patients, which represents 100% of eligible patients from known randomized trials.
Overall survival data were extracted from all but one of the trials (11). Four of the seven trials provided hazard ratios of death in the IP group and included covariates in Cox regression analysis (4,6,12,13). Most included age, tumor type and grade, performance status, and residual disease as covariates before commencing chemotherapy. Six trials displayed Kaplan-Meier survival curves (4,6-8,12,13), and we constructed a survival curve for the Zylberberg trial from individual patient data presented. One paper presented sufficient data to allow calculation of the hazard ratio using Parmar's methods (8). Hazard ratio of death for Kirmani and Zylberberg was estimated from the Kaplan-Meier survival curves.
Disease-free survival data and Kaplan-Meier disease-free survival curves were available from four trials. Two trials presented the calculated hazard ratios (4,6). Gadducci presented sufficient data to allow calculation using Parmar's methods (8), and the hazard ratio of recurrence for Kirmani's paper was estimated from the Kaplan-Meier disease-free survival curves (7). The definitions of recurrence varied amongst these trials. For example, Kirmani used the
Eastern Cooperative Oncology Group definition; Markman and Gadducci used date of entry to date of appearance of disease (clinical or radiological) or date of death from any cause. Seven of the eight included trials that reported adverse effects, with the exception of the trial by Zylberberg. Toxicity criteria included the Southwest Oncology Group, Common Toxicity Criteria, and the World Health Organization, all of which were comparable for the toxicities described. Gadducci used the WHO criteria, but included four grades of alopecia; therefore, these data could not be assimilated because the WHO criteria divide alopecia into only three grades. Quality of life scores were reported in the Armstrong trial using the Functional Assessment of Cancer Therapy scale, with General, Neurotoxicity, Pain, and Ovarian cancer subscales. This was reported at the 2004 annual American Society of Clinical Oncology meeting (14). Subgroup meta-analysis was not performed because data from the subgroups in the various studies were not adequate for meta-analysis. Only Alberts and Armstrong reported survival subgroup analysis including the group of patients with residual tumors <0.5 cm, but insufficient data were available in the Alberts paper to perform the meta-analysis (4,12). However, both suggest that IP chemotherapy is effective, irrespective of residual disease volume. Only the trial by Armstrong assessed QOL as an outcome measure; therefore, no meta-analysis was performed. Catheter-related complications of IP drug administration were discussed in all of the trials, but data retrieved from them were insufficient to produce a meta-analysis. An attempt was made to comprehensively document the numbers of, or reasons for, withdrawal from treatment protocol, but insufficient data were available to report this. A meta-analysis based on RR for withdrawal from treatment could not be performed.
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