Phase I study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762, PNU 152243) administered on a daily x3 schedule.

BACKGROUND: 3'-Deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762, PNU 152243) is a highly lipophilic doxorubicin derivative which possesses potent in vitro and in vivo antitumor activity. Previous phase I studies had been conducted using a single bolus every 28 days. PATIENTS AND METHODS: We conducted a phase I study of FCE 23762 on a daily x3 every 28 days schedule. Thirty patients received 68 cycles of therapy at 5 dose levels (200-600 micrograms/m2/d). RESULTS: Prolonged neutropenia and thrombocytopenia were the dose-limiting toxicities. Other nonhematological toxicities included nausea and vomiting, anorexia, fatigue and transient elevations of serum creatinine and hepatic transaminases. No cardiac toxicity was demonstrated. There were no partial or complete antitumor responses. CONCLUSION: The recommended phase II dose using the schedule defined in this study is 500 micrograms/m2/dx3.

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.

Chemotherapy, biologics, and chemoprevention as systemic therapies for head and neck cancer.

The role of chemotherapy in the management of patients with head and neck carcinoma is actively being investigated. Currently, chemotherapy is considered the standard of care for patients with recurrent or metastatic disease. Several single-agent and combination regimens have been used, demonstrating a partial response rate of 30% or less. The role of chemotherapy in the neo-adjuvant and adjuvant setting is less clearly defined. Concomitant chemoradiotherapy and rapid sequence alternating combined therapy have demonstrated a survival advantage in randomized trials. The degree of toxicities associated with these regimens, however, currently limits their use to clinical trials. Biologic therapy has been evaluated neo-adjuvantly and in recurrent and metastatic disease. Additional trials are needed before definitive conclusions can be made regarding its effectiveness and indications. The role of chemoprevention is rapidly expanding, with new agents and combinations currently in clinical trials.