Evidence-based research for intraperitoneal chemotherapy in epithelial ovarian cancer.

Intraperitoneal (IP) therapy is the administration of chemotherapy or biologic agents directly into the peritoneal cavity. A recent Gynecologic Oncology Group trial showed a survival advantage for women with advanced ovarian cancer and small residual disease after initial surgical staging and debulking who received IP therapy when compared to the standard IV regimen. The results prompted a National Cancer Institute announcement recommending the use of IP therapy in women who meet the criteria. This article describes the rationale for and underlying principles of IP therapy and summarizes the results of the three main clinical trials that led to the recommendation for incorporation of IP therapy into initial treatment of epithelial ovarian cancer.

Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group.

PURPOSE: The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy. MATERIALS AND METHODS: The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing. RESULTS: Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed. CONCLUSION: Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.

Treatment advances in ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer death among women. Although many patients respond to initial surgery and platinum-based chemotherapy regimens, recurrence is common, and many individuals require treatment with multiple agents. A number of drugs not cross-reactive with platinums or taxanes are effective as secondary treatment for women with recurrent ovarian cancer. For this reason, ovarian cancer now is considered a chronic disease with treatment aimed at control of disease, palliation of symptoms, and quality-of-life maintenance. Achievement of these goals requires selection of effective therapies (eg, liposomal preparations) that minimize toxicities and effectively manage both short- and long-term adverse reactions. Novel therapeutic approaches are aimed at increasing the efficacy and tolerability of therapy for patients with ovarian cancer. Some of these therapies include intraperitoneal drug administration designed to achieve higher drug concentrations at tumors as well as agents that target underlying disease processes (eg, anticancer vaccines, monoclonal antibodies directed against cancer antigens, gene therapy, and antiangiogenic treatments). This report reviews both current and developing approaches to the treatment of this malignancy.

Chemotherapy-induced peripheral neuropathy.

PURPOSE/OBJECTIVES: To review the literature documenting the scope, treatment, and prevention of chemotherapy-induced neuropathy. DATA SOURCES: Published abstracts, primary research literature, and textbook chapters. DATA SYNTHESIS: Recent improvements in the management of other treatment-related toxicities have led to peripheral neuropathy becoming a dose-limiting toxicity of commonly used chemotherapeutic groups such as platinols, vinca alkaloids, and taxanes. CONCLUSIONS: The nervous system has not been the focus of education or training for oncology nurses. Therefore, nurses' ability to educate patients regarding this aspect of their condition has been limited. IMPLICATIONS FOR NURSING: With its significant impact on quality of life, peripheral neuropathy treatment and prevention are important components in the care of patients with cancer.

Psychometric evaluation of two scales assessing functional status and peripheral neuropathy associated with chemotherapy for ovarian cancer: a gynecologic oncology group study.

PURPOSE/OBJECTIVES: To evaluate the psychometric properties of two adapted scales, one for functional status and one for peripheral neuropathy secondary to neurotoxic chemotherapy. DESIGN: Repeated measures methodologic design conducted within a Gynecologic Oncology Group (GOG) phase III clinical trial that randomly assigned patients with advanced epithelial ovarian cancer to cisplatin and cyclophosphamide or cisplatin and paclitaxel. SETTING: 8 GOG institutions participating in the GOG clinical trial. SAMPLE: 88 evaluable outpatients enrolled in the GOG clinical trial. Sample size at time 1 (T1) was 88 patients and at time 2 (T2) was 67 patients. METHODS: All scales were administered at T1 (prior to initiation of chemotherapy) and T2 (after six cycles of chemotherapy but prior to second-look laparotomy). Internal consistency reliability, criterion validity, and construct validity were evaluated, and clinical application was explored. MAIN RESEARCH VARIABLES: Self-reported peripheral neuropathy and functional status (comprised of physical function and role function subscales), the GOG performance status scale, and the GOG toxicity criteria. FINDINGS: Reliability coefficients at T1 were physical function = 0.83, role function = 0.96, and peripheral neuropathy = 0.91; at T2, they were physical function = 0.83, role function = 0.92, and peripheral neuropathy = 0.89. At T1, physical function and role function correlated positively with performance status. Peripheral neuropathy correlated positively with GOG toxicity criteria used at T2. Principal component factor analysis suggested that the functional status scale had a two-factor structure with factors representing general and specific mobility and that the peripheral neuropathy scale also had a two-factor structure with factors representing foot and hand neuropathy. CONCLUSIONS: The physical function, role function, and peripheral neuropathy scales have internal consistency, reliability, criterion validity, and construct validity. However, revision of the scales should address modification of specific questions and consider increasing the Likert scale from a four-point to a five- or seven-point scale to enhance clinical sensitivity and application. IMPLICATIONS FOR NURSING: With minor modifications, these scales should be useful in assessing physical function, role function, and peripheral neuropathy in patients who receive agents that may cause peripheral neuropathy.