Vinorelbine in pre-treated advanced head & neck squamous cell carcinoma. A phase II study.

BACKGROUND: There are few moderately active single-agents for the treatment of recurrent or metastatic head & neck cancer. Thus, the identification of novel active agents is warranted. We performed the present phase II trial to evaluate activity and toxicity of vinorelbine (VNB) in previously treated patients with advanced head & neck cancer. PATIENTS AND METHODS: 16 patients entered the study, 15 of whom were evaluable. The main characteristics were: M/F = 14/1; median age of 58 yrs (18-67); median PS (Karnofsky score) of 70 (60-100); primitive tumor sites were: oropharynx in 5; larynx in 4, hypopharynx in 3, rhynopharynx in 2, and oral cavity in 1 patient; initial clinical stage was IV in 9, III in 4 and II in 2 patients. Previous treatments were: cisplatinum with concurrent radiotherapy in 6 and cisplatinum + fluorouracil (for at least 2 cycles) in 9 patients. VNB was given at the dose of 20 mg/m2 i.v. infusion for 1 hr, weekly, for a minimum of 8 doses. Response and toxicity were evaluated after at least 8 doses of VNB. RESULTS: Overall, 139 courses of VNB were given (median 9, range 8-19). Objective responses were: partial response in 1 patient (6%); stable disease, lasting at least 2 months, in 4 patients (27%) and progression in the other 10 patients (67%). Three patients had a one week delay in subsequent courses due to severe hematological toxicity. Toxicities observed were: leucopenia of grade IV (W.H.O.) in 2 patients and of grade I-II in 12 patients; granulocytopenia of grade III in 1 patient and of grade IV in 2 patients; grade I-II anemia in 4 patients; grade II phlebitis in 3 patients; grade II constipation in 2 patients, grade I-II peripheral neuropathy in 3 patients, grade I-II nausea and vomiting in 4 patients, and grade II stomatitis in 2 patients. CONCLUSIONS: VNB, in this series of heavily pre-treated patients with head & neck cancer, did not reveal an antitumor activity of interest.

Treatment of locally advanced squamous-cell carcinoma of the head and neck with concurrent radiochemotherapy - randomized comparison of Cisplatin versus Carboplatin.

Several phase II studies have shown that concurrent chemotherapy and radiotherapy (RT) improves the response rates and locoregional control in patients with advanced, unresectable squamous-cell carcinoma of the head and neck (H&N). However, it is still unclear which is the drug of choice to be given with RT. We therefore conducted a randomized comparison of cisplatin (CDDP)-RT versus carboplatin (CRP)-RT in such patients. The two platinum compounds were given at equitoxic doses. The primary objective of the study was to compare the side effects and the response rates of the two regimens. Radiotherapy was given at conventional dosages, 2 Gy for 5 days every week for a total dose of 64 Gy with CDDP 80 mg/m2 or CRP 375 mg/m2 for three cycles on days 1, 21 and 42. At present 53 patients are entered in the study: 27 in the CDDP arm and 26 in the CRP. The two arms were balanced for all the pre-treatment characteristics. Both the schedules were well tolerated. However, incidence of nausea and vomiting (p=0.0045); anemia (p=0.032) and peripheral neuropathy (p=0.032) was significantly greater with CDDP-RT as compared to CRP-RT. On the other hand, CRP-RT gives a significantly higher incidence of stomatitis (p=0.0067) and a marginally worse thrombocytopenia (p=0.09). The complete response (CR) rates were similar in the two arms (55.5% in the CDDP-RT versus 61.5% in that CRP-RT, respectively) as well as the overall response rates (92.5% versus 84.5%, respectively; p=0.36). The estimated 1 -and 2 year overall and disease-free survival rates were not significantly different in the two arms. In both the groups logistic-regression models showed that those patients with a CR (p=0.017); stage III (p=0.011); smaller primary (p=0.025) and limited node-involvement (p<0.001) had a significant better survival. We conclude that concurrent chemo-radiotherapy is an effective and safe treatment for patients with locally advanced H&N cancer. The combination CRP-RT possess a similar activity but a different, and perhaps a more favorable, spectrum of toxicity when compared to the CDDP-RT therapy. Survival results need to be assessed in a larger series and followed for a more prolonged time.

Synchronous radiotherapy and chemotherapy with cisplatin in the management of locally advanced or recurrent head and neck cancer.

A synergism between cisplatin and radiotherapy has been demonstrated in in vitro and in vivo studies. To improve the locoregional control of disease and the survival rate in patients affected by locally advanced or recurrent squamous cell carcinoma of the head and neck, we planned a Phase II study of concurrent radiotherapy, 2 Gy for 5 days every week for a total dose of 60-70 Gy with cisplatin 80 mg/m2 every 21 days for 2 or 3 doses (on days 1, 21, 42). Fifty-one patients were entered in the study; 48 were evaluable for response and toxicity; 18 (37.5%) had untreated Stage III disease; 25 (52%) had Stage IV disease; 5 (10.5%) had recurrent disease. The complete response rate in Stage III-IV patients was 63% (27 of 43) with 95% confidence limits from 48 to 77% (+/- 14.5%). In the group of five patients with recurrent disease, only one (20%) achieved a complete response. In patients with Stage III-IV disease, a significantly higher complete response rate was observed for those younger than 58.5 years (p = 0.05). The overall estimated 1- and 2-year survival was 59% and 37%, respectively, and a significantly better survival was observed in complete responders compared to partial responses or patients with stable disease (p = 0.037). Disease-free survival was 46% and 36% at 1 and 2 years, respectively. Distant failure occurred only in 12.5% of the patients. Overall, the treatment was well tolerated, and only three patients refused to complete the planned therapy. Gastrointestinal and hematological toxicity were the most common side effects. Data from present trial were compared with that of 50 patients with comparable characteristics treated with radiotherapy alone from 1985 to 1987 as a historical control. The complete response rate, the disease-free survival, and the overall survival appear to be better in the patients treated with chemoradiotherapy. It was concluded that the combination of chemoradiotherapy in patients with Stage III-IV head and neck squamous cell carcinoma is an effective and safe treatment with an apparent better locoregional control than radiotherapy alone. Survival results need to be evaluated in a Phase III randomized trial.

Italian experience of voice restoration after laryngectomy with tracheoesophageal puncture.

This report concerns 102 cases of tracheoesophageal puncture performed as a means of secondary voice restoration after total laryngectomy, in 70 patients proving unable to learn esophageal speech and as a treatment of choice in a further 32 cases. Complications arose in 21 cases but were generally minor and could be overcome. Results were favorable in 45 of 70 and 29 of 32 cases, respectively. The method was considered effective, particularly when supported by the patient's determination to learn a verbal communication method.

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck.

A synergism between cis-platinum (CDDP) and radiotherapy (RT) has been demonstrated both in culture systems and in clinical studies. On the above basis, we planned, in patients with locally advanced or unresectable squamous cell carcinoma of the head and neck, a concomitant treatment with CDDP 80 mg/m2 i.v. every 3 weeks for three doses (days 1, 21 and 42) and RT in the primary and in the neck nodes bilaterally, for a total dose of 60-70 Gy. Thirty-five untreated patients with poor prognosis unresectable stage II and stages III-IV disease were entered in the study and 32 were evaluable. Complete response (CR) rate was 75% (24/32) with 95% confidence limits from 60 to 90% (+/- 15%): 8 cases (25%) achieved a partial response, for an overall response rate of 100%. A significantly higher CR rate and a longer survival rate was observed in patients with good performance status (PS = 90-100) and stages II-III. The overall estimated 2-year survival is 46%; 59% for patients who obtained a CR versus 0% for those who achieved only a partial response. Overall the treatment was well tolerated and gastrointestinal and hematologic toxicities were the most common side effects. In conclusion, the combination of CDDP plus RT is a very effective and safe treatment and we recommend such an approach in head and neck squamous cell carcinoma, particularly in those patients with good PS and with unresectable stage II or stage III disease.