5-Fluorouracil dose intensification and granulocyte-macrophage colony-stimulating factor in cisplatin-based chemotherapy for relapsed squamous cell carcinoma of the head and neck: a phase II study.

A previous phase I study showed that in a 5-day combination of cisplatin (CDDP) 20 mg/m2/day and 5-fluorouracil (5-FU) intravenous bolus, the maximum tolerable dose of 5-FU is 200 mg/m2/day without the use of growth factors and 300 mg/m2/day with recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) support. In the present phase II study, 26 patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated with CDDP, 20 mg/m2/day, and 5-FU, 300 mg/m2/day intravenous bolus, for 5 consecutive days every 3 weeks. Granulocyte-macrophage colony-stimulating factor, 5 mg/kg/day subcutaneously, was administered from days 8 to 19. All patients had previously undergone surgery and/or radiation treatment. None had previously received chemotherapy. Mucositis (19% of the patients) and thrombocytopenia (42%) were the most frequent, but generally mild, toxicities. Relevant, GM-CSF-related side effects were detected in 12% of the patients. The median number of cycles delivered was four. Three complete and five partial responses were recorded (31% overall response rate). Further investigation of this regimen is unwarranted because of both its lack of improvement in antitumoral activity and the high costs incurred with the use of growth factors.

In vivo cell kinetics in elderly patients affected by squamous cell carcinoma of the head and neck.

The purpose of the study was to determine whether pretreatment tumor cell kinetics can predict local control in elderly patients affected by squamous cell carcinoma of the head and neck (SCC-HN) and help guide different therapeutic modalities. Over a 6-year period, 52 patients with stage II to IV SCC-HN and aged more than 70 years were given an infusion of bromodeoxyuridine (BrdUrd) 6 hours prior to tumor biopsy sampling. The simultaneous labeling S phase fraction (LI) and duration (Ts) as well as potential doubling time (Tpot) were measured with flow cytometric analysis of BrdUrd and DNA content. Patients were then treated as follows: 14 with conventional radiotherapy; 13 with partly accelerated radiotherapy; 11 with chemoradiotherapy; 14 with surgery plus adjuvant radiotherapy. Univariate analysis showed that, independently of treatment type, patients with fast growing SCCs-HN characterized by Tpot value < or = 5 days had a lower three-year local control than patients with slow growing tumors with Tpot value > 5 days. Our results also demonstrated that surgery or chemoradiotherapy were effective treatments for fast growing tumors. Radiotherapy alone, instead, was more effective for slow growing tumors. Our data suggest that in vivo cell kinetics may play a role as additional prognostic factor for elderly patients with SCC-HN and predict the outcome of different treatments.

Chemoradiotherapy as an alternative to radiotherapy alone in fast proliferating head and neck squamous cell carcinomas.

The aim of this pilot study was to explore the prognostic relevance of cell kinetics parameters on the local control of patients affected by head and neck squamous cell carcinoma (HN-SCC), randomly assigned to receive either alternating chemoradiotherapy or partly accelerated radiotherapy. Between 1992 and 1995, 40 patients with HN-SCC at stages III and IV entered the study. Multiple primary tumor biopsies were obtained 6 h after in vivo infusion of bromodeoxyuridine, an analogue of thymidine that is incorporated in DNA-synthesizing cells. In vivo S-phase fraction labeling index (LI), duration of S-phase (TS), and potential doubling time (Tpot) were obtained by analysis of the flow cytometric content of bromodeoxyuridine and DNA. Twenty patients were treated by alternating chemotherapy and conventional radiotherapy (arm A), whereas 20 other matching patients received partly accelerated radiotherapy alone (arm B). Univariate local control analysis showed that LI, TS, and Tpot were not prognostically significant in either arm. However, local control probability at 2 years for fast growing tumors, characterized by a LI of 9%, was higher for patients treated with alternating chemoradiotherapy than it was for those treated with partly accelerated radiotherapy alone (68 versus 39%). Conversely, local control probabilities for slow proliferating tumors (LI, <9%) treated in the two arms were similar. These results suggest a potential role for alternating chemotherapy and radiotherapy in HN-SCC patients with fast growing tumors.