INTENSIFIED CHEMOTHERAPY WITH GRANULOCYTE-MONOCYTE COLONY-STIMULATINGFACTOR PROTECTION IN ADVANCED, RELAPSED SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - A PHASE-I STUDY

Background: The administration of granulocyte-monocyte colony stimulat ing factor (GM-CSF) should allow an increase in the doses of chemother apy for patients with advanced cancers of the head and neck. Patients and methods. Eleven patients with histologically proven relapsed squam ous cell carcinoma of the head and neck entered this Phase I study bas ed on the combination of cisplatin (20 mg/m(2)/day for 5 days), escala ting doses of 5-fluorouracil, both given by intravenous injection from day 1 to 5, and GM-CSF, 5 mu g/kg from day 8 to day 19. Results: The maximum tolerated 5-fluorouracil dosage was 300 mg/m(2) i.v. bolus for 5 consecutive days q. 3 weeks. Thrombocytopenia was the limiting fact or to further increase of 5-fluorouracil dosage. Moderate to severe st omatitis were quite rare despite the increased dose of the antimetabol ite. GM-CSF was well tolerated: no significant local or systemic side effects attributable to this drug were recorded. Conclusions: Adding G M-CSF to the combination of cisplatin and 5-fluorouracil allowed to in crease fi-fluorouracil dose up to 50% over the conventional dosage. Fu rther increase of the dose was precluded by the development of severe thrombocytopenia.