Secondary surgical cytoreduction for advanced ovarian carcinoma.

BACKGROUND: We evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery. METHODS: Women were enrolled within six weeks after primary surgery. If, after three cycles of postoperative paclitaxel plus cisplatin, a patient had no evidence of progressive disease, she was randomly assigned to undergo secondary cytoreductive surgery followed by three more cycles of chemotherapy or three more cycles of chemotherapy alone. RESULTS: We enrolled 550 women. After completing three cycles of postoperative chemotherapy, 216 eligible patients were randomly assigned to receive secondary surgical cytoreduction followed by chemotherapy and 208 to receive chemotherapy alone. Surgery was declined by or medically contraindicated in 15 patients who were assigned to secondary surgery (7 percent). As of March 2003, 296 patients had died and 82 had progressive disease. The likelihood of progression-free survival in the group assigned to secondary surgery plus chemotherapy, as compared with the chemotherapy-alone group, was 1.07 (95 percent confidence interval, 0.87 to 1.31; P=0.54), and the relative risk of death was 0.99 (95 percent confidence interval, 0.79 to 1.24; P=0.92). CONCLUSIONS: For patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal, the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival.

Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS: Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

A phase II trial of pyrazoloacridine (PZA) in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

PURPOSE: The Gynecologic Oncology Group performed a phase II study to determine the response rate to pyrazoloacridine (PZA) in patients with advanced, persistent or recurrent squamous carcinoma of the cervix. METHODS: PZA was administered intravenously over 3 h every 3 weeks. A dose of 760 mg/m(2) was given to the first 11 patients and was reduced to 560 mg/m(2) for subsequent patients. The dose reduction was undertaken because of unexpected severe neutropenia among the initial patients. RESULTS: Among 24 evaluable patients, 21 of whom had prior chemotherapy, there was one, brief, complete response (4.2%) and no partial responses. The major toxicity was neutropenia. CONCLUSION: PZA at the dose and schedule employed, has insignificant activity in this population.

Fatigue and gynecologic cancer.

Fatigue is common in women with gynecologic cancers and is thought to be multifactorial. Anemia, cachexia, pain, and depression are frequently associated with cancer and treatment-related fatigue and should be evaluated and treated. The National Comprehensive Cancer Network Fatigue Practice Guidelines are helpful in the assessment and treatment of women with gynecologic cancer-related fatigue.

Expression of a retinol dehydrogenase (hRoDH-4), a member of the retinol/steroid dehydrogenase family implicated in retinoic acid biosynthesis, in normal and neoplastic endometria.

OBJECTIVE: Retinoic acid plays an essential role in epithelial differentiation, and retinoid homeostasis is disrupted in cancers of epithelial origin. The goal of this study was to determine whether hRoDH-4, an enzyme that can catalyze the first and rate-limiting step in retinoic acid biosynthesis, is expressed in normal endometrium and, if so, whether its expression is altered in endometrial cancer. STUDY DESIGN: Proliferative, secretory, hyperplastic, and neoplastic endometria were examined by immunocytochemistry for hRoDH-4 protein and by reverse transcriptase-polymerase chain reaction for the hRoDH-4 transcript. RESULTS: In proliferative and secretory glandular epithelia, immunoreactive hRoDH-4 was uniformly present. In endometrial cancers, hRoDH-4 immunoreactivity was markedly reduced in many neoplastic epithelial cells. Expression of hRoDH-4 in normal and neoplastic endometrium was confirmed by findings on reverse transcriptase-polymerase chain reaction. CONCLUSION: These findings are consistent with the hypothesis that altered expression of enzymes essential for in situ retinoic acid biosynthesis is an important phenotypic change associated with the development of endometrial cancer.

Cisplatin as second-line therapy in ovarian carcinoma treated initially with single-agent paclitaxel: a Gynecologic Oncology Group study.

OBJECTIVES: The platinum compounds are the most active agents in the treatment of ovarian carcinoma. Phase II trials demonstrated the activity of paclitaxel in patients with disease clinically resistant to platinum-based front-line therapy, and phase III studies confirmed that a combination of paclitaxel plus a platinum was superior to cyclophosphamide plus a platinum. This study evaluated the activity of platinum in patients with bulky advanced disease treated with single-agent paclitaxel as front-line therapy on a Gynecologic Oncology Group protocol. Those patients who had persistent (stable) or progressive disease while receiving paclitaxel, or a recurrence of disease within 6 months of completing six cycles of paclitaxel therapy, received single-agent cisplatin. METHODS: Thirty-nine eligible patients with ovarian carcinoma persistent, progressive, or recurrent after initial treatment with paclitaxel 200 mg/m(2) over 24 h every 3 weeks received cisplatin 100 mg/m(2) every 3 weeks until disease progression or unacceptable toxicity. RESULTS: Among 37 patients evaluable for response, 8 complete (22%) and 13 partial (35%) responses resulted. Twelve (32%) patients exhibited stable disease, while 4 (11%) had increasing disease. Median progression-free survival was 11.0 months. Median survival was 15.0 months. All but two patients were clinically resistant to paclitaxel (progression during or within 6 months after completion of paclitaxel). Grade 2 or worse adverse effects among 39 patients evaluable for toxicity included neutropenia (23), thrombocytopenia (3), anemia (10), nausea and vomiting (23), azotemia (7), neurotoxicity (9), fever (2), and tinnitus (1). CONCLUSION: These data provide evidence that cisplatin is active as second-line therapy in patients clinically resistant to paclitaxel. The overall response rate is high (57%) with excellent progression-free and overall survival in the second-line setting.