Phase I trial of concomitant vinorelbine, paclitaxel, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies.

OBJECTIVE: The aim of this study was to determine the feasibility and toxicity of concomitant vinorelbine, paclitaxel, and pelvic radiation therapy (RT) in patients with advanced cervical cancer and other pelvic malignancies. METHODS: Eligible patients included those with large or locally advanced cervical cancer. In addition, patients with other advanced gynecologic malignancies were eligible. In part I, vinorelbine was administered as a single agent during pelvic RT at a starting dose of 10 mg/m(2)/week with subsequent cohorts being escalated in 5 mg/m(2)/week increments. In part II, paclitaxel was added to vinorelbine (20 mg/m(2)/week) and pelvic RT at a starting dose of 20 mg/m(2)/week. RESULTS: Thirty-three women with pelvic malignancies (22 cervix, 6 vagina, 3 endometrium, 2 vulva) were enrolled. Twenty-seven received vinorelbine and 6 received both paclitaxel and vinorelbine in combination with pelvic RT. Escalating vinorelbine doses to 25 mg/m(2)/week were well tolerated, with the primary toxicity being hematologic. RT was delayed in only 1 patient due to acute hematologic toxicity. In contrast, the combination of paclitaxel, vinorelbine, and pelvic RT was not well tolerated. Five of 6 patients (83%) experienced grade > or = 2 leukopenia, with 2 patients missing > 1 cycle of chemotherapy. Moreover, RT was delayed for 1 week in 2 of 6 patients (33%). CONCLUSIONS: Concomitant pelvic RT and vinorelbine with doses to 25 mg/m(2)/week is well tolerated. The addition of paclitaxel to this combination is associated with significant hematologic toxicity and is thus not a feasible approach.

Absence of major peripheral neuropathy in a phase II trial of ifosfamide with vinorelbine in patients with ovarian cancer previously treated with platinum and paclitaxel.

Both ifosfamide and vinorelbine have been shown to produce responses in women with previously treated ovarian cancer. However, vinorelbine has been reported to cause severe neuropathy in patients previously treated with paclitaxel. We assessed a regimen consisting of ifosfamide 1.6 g/m2/d and vinorelbine 30 mg/m2/d for 3 days consecutively every 21 days. Because these doses resulted in severe neutropenia despite the use of granulocyte colony-stimulating factor, doses were reduced to a final level of ifosfamide 960 mg/m2/d and vinorelbine 20 mg/m2/d. Peripheral sensory neuropathy was evaluated by questionnaire. A total of 30 women were treated. All had previously been treated with both a platinum compound and paclitaxel. One partial response was observed among 23 patients with measurable disease, and two CA-125 responses were noted among seven patients without measurable disease. Severe progressive neurotoxicity was not observed. Despite the fact that almost half the patients had not been exposed to cyclophosphamide, this regimen produced few responses. Superior response rates have been reported with single-agent vinorelbine at doses that do not require growth factor support. With this dose and schedule, vinorelbine is reasonably safe therapy for patients who have received prior paclitaxel and who have have mild baseline sensory neuropathy.

Phase II study of 96-hr continuous-infusion etoposide and doxorubicin with bolus cyclophosphamide in refractory epithelial ovarian cancer.

Effective salvage chemotherapy for patients with ovarian cancer who have failed platinum- and taxane-based regimens has not been identified. It has been reported that prolonged infusions of chemotherapy may be active in some malignancies which have become refractory to bolus treatments. We evaluated a regimen of 96-hr continuous-infusion doxorubicin (10 mg/m2/24 hr), etoposide (50 mg/m2/24 hr), and bolus cyclophosphamide (750 mg/m2) administered every 21 days to patients with ovarian cancer who had previously been treated with paclitaxel and a platinum compound. Nineteen women were treated, 15 of whom had platinum-refractory cancer. Six of the first 9 experienced a neutropenic fever after the first treatment cycle, and therefore all subsequent patients received prophylactic granulocyte-colony-stimulating factor. Other significant toxicities included hand and foot syndrome (1 patient) and mucositis (4 patients). There was one partial response in a patient with platinum-sensitive disease. We conclude that this regimen causes significant myelosuppression and does not have major activity in heavily pretreated patients with ovarian cancer.

Assessing health differences in an elderly population: a five-year follow-up.

A sample of several hundred elderly residents of Alameda County was recontacted after 5 years to determine the effects over time of different social support and demographic variables on health status. The follow-up investigation demonstrated a strong relationship between respondents' social support resources in 1980 and their subsequent self-rated health. Indeed, social contacts in 1980, together with age and financial need, enabled us to correctly "predict" respondents' subsequent health status in close to two-thirds of the cases. As anticipated, however, the variable most strongly associated with self-rated health in the earlier cross-sectional study--illness of a mate during the preceding 6 months--disappeared as a predictor variable in the longitudinal study. This finding is in keeping with the literature on bereavement and other stressful life events which demonstrates that the health impact of such stressors is in most cases time-limited. The study findings support earlier research demonstrating the important role of social support for health maintenance and disease prevention in the elderly. They further underscore the need for intervention strategies designed to strengthen the network resources of those elders at high risk for social isolation.

The significant of an ill spouse for assessing health differences in an elderly population.

In a survey of 678 elderly residents of Alameda County, California, it was found that respondents who reported their spouses as being ill in the last six months were more likely to report their own health as poor than those respondents whose spouses were not previously ill. The spouse's health was found to be the best predictor of the respondent's health. Research in this area may lead to a better understanding of the elderly spouse as a source of social support and may provide geriatricians with new insights into the health risks facing the married elderly.

Supportive exchange: an exploration of the relationship between social contacts and perceived health status in the elderly.

While social ties are known to bear an important relationship to health status among the elderly, the components of that association remain unclear. This study explored the hypothesis that 'supportive exchange', or the giving and seeking of advice and other forms of assistance, bears an important relationship to perceived health status. Six-hundred and seventy-eight elderly residents of Alameda County, CA, participated in this survey research study, which examined social ties, supportive exchange, and health status. A strong relationship was found between a key dimension of supportive exchange - the giving and seeking of advice - and self-reported health status. The association between advice seeking and health status was particularly high, demonstrating that advice seeking may be as strongly associated with health status as social ties. While it is important to develop refined indices for the measurement of other dimensions of supportive exchange, this exploratory study suggests that the concept may be a useful one in furthering research on the relationship between health status and social contacts among the elderly.