Prognostic factors for response to cisplatin-based chemotherapy in advanced cervical carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: Cisplatin-based combination chemotherapy is considered standard treatment for advanced/recurrent cervical carcinoma; however, the majority of patients do not respond. This study was undertaken to identify the prognostic factors and develop a model predictive of (non-) response to chemotherapy. METHODS: Four-hundred twenty-eight patients with advanced cervical cancer who received a cisplatin-containing combination in three Gynecologic Oncology Group (GOG) protocols (110, 169 and 179) were evaluated for baseline clinical characteristics and multivariate analysis was conducted to identify factors independently prognostic predictive of response using a Logistic regression model. A predictive model was developed and externally validated using an independent GOG protocol (149) data. RESULTS: Multivariate analysis identified five factors (African-American, performance status [PS] >0, pelvic disease, prior radiosensitizer and time interval from diagnosis to first recurrence <1 year) independently prognostic of poor response. A simple prognostic index was derived based on the total number of risk factors. When patients were classified into three risk groups (low risk: 0-1 factor; mid risk: 2-3 factors; high risk: 4-5 factors), patients with 4-5 risk factors were estimated to have a response rate of only 13%, and median progression-free and overall survival of 2.8 months and 5.5 months, respectively. The accuracy of the index was supported by both internal and external datasets. CONCLUSIONS: A simple index based on five prognostic factors may have utility in clinical practice to identify the women who are not likely to respond to the cisplatin-containing regimens. This subgroup of patients should be considered for non-cisplatin chemotherapy or investigational trials.

Progress in gynecologic cancer research: the Gynecologic Oncology Group experience.

Since 1970, the Gynecologic Oncology Group (GOG) has been a leader in clinical research in female pelvic cancers. Currently comprising 59 institutions and their affiliates in the United States, Canada, and elsewhere, the GOG has defined, principally through phase III randomized clinical trials, the standard of care for several stages and types of gynecologic cancer. This review will briefly summarize, in the context of research done concurrently by other groups and institutions, important GOG trials that have moved the field forward, especially in ovarian, endometrial, and cervical cancers. The role of cisplatin, carboplatin, and paclitaxel, as well as other drugs and combinations, in gynecologic cancer has been extensively studied by the GOG, as has chemoradiation in cervical cancer. Surgical staging of cervical and endometrial cancers has provided new insights and guidance for management. The benefits and limitations of radiation therapy in these diseases have been examined carefully. Thus, the stage has been set for further progress in this field.

Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer: an intergroup study.

PURPOSE: To determine if increasing the dose of paclitaxel increases the probability of clinical response, progression-free survival, or overall survival in women who have persistent or recurrent ovarian cancer, and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever. PATIENTS AND METHODS: Consenting patients with persistent, recurrent, or progressing ovarian cancer, despite first-line platinum therapy (but no prior taxane), were randomly assigned to paclitaxel 135 mg/m2, 175 mg/m2, or 250 mg/m2 over 24 hours every 3 weeks. Patients receiving paclitaxel 250 mg/m2 were also randomly assigned to 5 or 10 microg/kg of filgrastim per day subcutaneously. RESULTS: Accession to the paclitaxel 135-mg/m2 arm was closed early. Among the 271 patients on the other regimens with measurable disease, partial and complete response on paclitaxel 250 mg/m2 (36%) was significantly higher than on 175 mg/m2 (27%, P =.027). This difference was more evident among patients who never responded to prior platinum. However, progression-free and overall survival results were similar. The median durations of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m2 and 250 mg/m2, respectively. Thrombocytopenia, neuropathy, and myalgia were greater with paclitaxel 250 mg/m2 (P <.05). The incidence of neutropenic fever after the first cycle of paclitaxel 250 mg/m2 was 19% and 18% on the 5-microg/kg and 10-microg/kg filgrastim dose, respectively (22% for paclitaxel 175 mg/m2 without filgrastim). CONCLUSION: Paclitaxel exhibits a dose effect with regard to response rate, but there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m2 plus filgrastim. Doubling the filgrastim dose from 5 to 10 microg/kg did not reduce the probability of neutropenic fever after high-dose paclitaxel.

Advances in the treatment of gynecologic malignancies. Part 1: Cancers of the cervix and vulva.

Two recent multicenter randomized trials have greatly advanced our understanding of the role of postoperative radiation therapy in operable cervical cancer. In locally advanced cervical cancer, such studies have shown a significant improvement in survival with the use of concurrent cisplatin-based chemoradiotherapy and have redefined standard therapy for women with this presentation. In vulvar cancer, adjuvant chemoradiotherapy is emerging as an effective therapeutic approach, permitting less morbid surgery. Although the results of treatment with concurrent chemoradiotherapy are encouraging in both cervical and vulvar cancer, efforts to minimize the associated toxicity are needed.

Advances in the treatment of gynecologic malignancies. Part 2: Cancers of the uterine corpus and ovary.

Over the past few decades, we have gained a better understanding of the risk factors associated with the recurrence of endometrial cancer. Adjuvant postoperative radiotherapy in an intermediate-risk group of endometrial cancer patients resulted in improvement in local control, but survival was not improved significantly. Postoperative management of uterine sarcomas remains investigational. The management of ovarian cancer has notably advanced during the 1990s. Platinum- and paclitaxel-based combination chemotherapy set a new standard of care for patients with advanced ovarian cancer. During the late 1990s, a trend emerged favoring the use of carboplatin over cisplatin for first-line management of advanced ovarian cancer because of its more favorable safety profile. Adjuvant therapy for early-stage high-risk ovarian cancer continues to be actively investigated.