Methotrexate, vinblastine, epidoxorubicin, and bleomycin as second-line chemotherapy for recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Thirty evaluable patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck region previously treated with cisplatin-based chemotherapy were treated with a combination of methotrexate, vinblastine, epidoxorubicin, and bleomycin as second-line chemotherapy. Besides surgery and/or radiotherapy all patients had previously received chemotherapy as induction therapy or as palliation for recurrent disease. Only 20% of patients achieved a partial objective response with a mean duration of 5.6 months (range 3.2-6.2), and 30% of patients had a stabilization of disease with a mean duration of 4.2+ months (range 3.8-6.0). Patients who responded had rhinopharyngeal carcinoma, poorly differentiated histology, or they had not been previously treated with radiotherapy. All remaining patients (50%) progressed. Toxicity was significant with grade 3-4 leukopenia in 30% of cases, grade 2-3 mucositis in 40% of patients, and grade 2-3 vomiting in 43% of cases. In consideration of the dismal clinical results and of the significant toxicity recorded, we do not recommend to use this combination as second-line therapy in recurrent head and neck cancer. Further chemotherapy should be reserved to carefully selected cases with a reasonably high chance of response.

A phase II study of levofolinic acid and 5-fluorouracil plus cisplatin in patients with advanced head and neck squamous cell carcinoma.

Forty patients with advanced squamous cell carcinoma of the head and neck (SCHNC) were treated with a combination of levofolinic acid 100 mg/m2+5-fluorouracil 375 mg/m2 in a 4-hour infusion plus cisplatin 20 mg/m2 in a 2-hour infusion for 5 consecutive days, repeated every 21-28 days. In the group of 20 previously untreated patients, a 90% overall response rate (ORR) with a 30% complete response rate (CRR) was obtained. In the group of 20 pretreated patients with recurrent and/or metastatic SCHNC, a 55% ORR with 15% CRR was achieved. This treatment was given on an outpatient basis and was generally very well tolerated with only 2 patients requiring hospitalization. Grade 1-2 gastrointestinal and hematological side effects were the most frequent toxicities. One patient had grade 4 liver toxicity, 1 had grade 4 anemia, and 1 grade 3 neurotoxicity. This treatment seems very active in both previously untreated and pretreated patients. However, in the latter group the mean duration of complete response (12.2+ months) and of partial response (7.4+ months) are, in our opinion, still unsatisfactory.

Hydroxyurea modulates 5-fluorouracil antineoplastic activity in advanced head and neck carcinoma pretreated with chemotherapy.

After informed consent 21 patients with advanced head and neck cancer resistant to folinic acid/5-fluorouracil (FA/5FU + cisplatin) were treated with weekly FA/5FU plus low dose hydroxyurea (HU) to evaluate if HU could further modulate 5FU antineoplastic activity. Five patients achieved a partial response (23.8%) which was short-lived (mean duration 6.5 months). Three patients (14%) had stable disease and 13 (62%) progressed. Among responders, four patients had epidermoidal carcinoma and one had clear cell carcinoma. Treatment was well tolerated and 5FU-related toxicity was not apparently worsened by the addition of HU. The most frequent toxicities were nausea/vomiting (81%), diarrhea (52%) and leukopenia (57%). Grade 3 nausea/vomiting and leukopenia were recorded in only 19 and 9% of cases, respectively. One patient had grade 1 cutaneous toxicity and a second patient showed a hand-foot syndrome. These results suggest that HU may further positively modulate 5FU antineoplastic activity.

Weekly 5-fluorouracil and folinic acid plus escalating doses of cisplatin with glutathione protection in patients with advanced head and neck cancer.

Twenty-two patients with advanced head and neck carcinoma were treated with 5FU 400 mg-2 m-1 week and folinic acid 500 mg m-2 week-1 plus CDDP in escalating doses from 20 to 40 mg m-2 week-1 without forced diuresis. Reduced glutathione at the dose of 1.5 g m-2 was employed to protect patients from CDDP-related nephrotoxicity. The aims of the study were: a) to evaluate the therapeutic efficacy of this schedule, and b) to evaluate reduced glutathione as uroprotector. Out of 20 evaluable patients 14 (70%) had a major objective response. A CR with a mean duration of 9.0+ months was achieved in 15% of the patients, a PR of 5.8+ months in 55% of the patients, while 3 patients had stable disease and 4 progressed. It was possible to escalate CDDP up to 35 mg m-2 week-1, but at the dose of CDDP 40 mg m-2 week-1 the occurrence of grade 2 renal toxicity provoked a severe reduction of dose-intensity. Overall, this treatment has been very well tolerated by most patients with few cases of grade 3 gastrointestinal or hematological toxicity. In conclusion, the schedule seems effective and may be safely given to patients with advanced head and neck cancer on outpatient basis. Reduced glutathione seems to be able to reduce, at least partially, CDDP-related nephrotoxicity permitting the delivery of higher CDDP doses.