PURPOSEUsing the technique of meta-analysis, we aim to illustrate the potential benefit, or lack of it, in adding chemotherapy to locoregional definitive treatment in a prospective randomized setting.PATIENTS AND METHODSMantel-Haenszel summary analyses were used to test 42 prospective and properly randomized trials for statistically significant differences in the proportion with side effects and in the proportion with response to treatment between the experimental treatment arm (including chemotherapy) and control arm (local definitive treatment only) of the study. Summarized estimates of relative risks of side effects and relative proportions of positive responses were obtained using the summarizing options in PROC FREQ in the SAS computer package. In 25 of 42 studies, sufficient survival information was available to estimate the effect of chemotherapy on the rate of dying per person per unit of time.RESULTSChemotherapy, when added to local definitive treatment, was found to increase toxicity. This incre...

Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region. A meta-analysis of prospective and randomized trials.

In a series of three consecutive pilot studies carried out between 1977 and 1981 at Wayne State University, Detroit, Michigan, designed to test the feasibility of multimodality therapy in patients with previously untreated advanced squamous cell carcinoma of the head and neck, patients received three different induction chemotherapy regimens: cisplatin + Oncovin (vincristine) + bleomycin (COB) for two courses; 96-hour 5-fluorouracil (5-FU) infusion and cisplatin for two courses, or 120-hour 5-FU infusion + cisplatin for three courses. Over-all response rates (complete response + partial response) to each of the three induction chemotherapy regimens were high: 80%, 88%, and 93%, respectively. Superior complete response rate in the group receiving three courses of 120-hour 5-FU infusion + cisplatin was 54% versus 29% for COB and 19% for two-course 96-hour 5-FU infusion + cisplatin (P = 0.04). Significant survival advantage at 18 months minimum follow-up for the group receiving three courses of 120-hour 5-FU + cisplatin induction therapy was found. Actual T and N stage may influence the clinical complete response rate. Responders to initial chemotherapy have significantly better survival as compared to nonresponders regardless of subsequent surgery and/or radiotherapy. These studies show that a multimodality approach to management of advanced head and neck cancer is feasible. Superior complete response rate and survival in one of the treatment groups suggest that choice of induction chemotherapy regimens and/or number of courses is of prime importance in such multimodality treatment programs.

Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin.

SQUAMOUS-CELL carcinoma of the head and neck accounts for five per cent of the cases of cancer in the United States. Only one third of patients with this neoplasm present with localized disease easily curable by surgery and radiation. These treatment methods, however, have not provided adequate tumor control in the majority of patients who present with advanced local and regional disease. Local recurrences occur in up to 60 per cent of these patients, and distant metastases develop in 20 to 30 per cent; survival remains poor (0 to 40 per cent).1 , 2 Until recently, chemotherapy has been reserved only for . . .

Chemotherapy in head and neck cancer.

The combination of cisplatin and 96-hour infusion of 5-fluorouracil (5-FU) was evaluated in 30 patients with recurrent (local and regional) and disseminated histologically proven epidermoid cancer of the head and neck who failed surgery and radiotherapy. Cisplatin 100 mg/M2 intravenous (IV) bolus was given on day 1 with hydration and mannitol diuresis; 5-FU 1000 mg/M2 per day for 96-hour infusion was started immediately after cisplatin on day 1. All patients had measurable lesions. Eight (27%) patients achieved complete response (CR), and 13 (43%) had partial response (PR). Overall response rate was 70% (8 of 30 CR and 13 of 30 PR). Response rate in patients with recurrent local and regional disease was 89% (17/19) with median survival of 32 weeks, while response in patients with disseminated disease was 36% (4/11) with median survival of 24 weeks. Patients with good performance status (PS) (greater than or equal to 70%) had a response rate of 79% (19/24), while those with poor PS (less than 70%) had a response rate of 33% (2/6). Seven patients with recurrent disease who had a response to this chemotherapy went to further salvage surgical procedures. It is concluded that the combination of cisplatin and 5-FU is very effective and well tolerated in these patients, and leads to further salvage in some patients with improved longevity and quality of life.

Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck

This study examines the role of combination chemotherapy with surgery and/or radiotherapy in the initial treatment of patients with advanced stage III and IV squamous-cell carcinoma of the head and neck (SCCHN). Two courses of initial (induction) cisplatin, bleomycin, and methotrexate with oral calcium leucovorin (PBM) were used with the principal intent of increasing the effectiveness of subsequent surgery and/or radiotherapy. Following induction chemotherapy and local treatment, disease-free patients who had responded to initial chemotherapy were entered into a randomized trial of adjuvant PBM. The response rates to induction PBM chemotherapy were a complete response (CR) rate of 26% and a partial response (PR) rate of 52%, for an overall response rate of 78%. A response to induction PBM was highly correlated with failure-free survival (P less than .0001). A Cox multistep regression analysis of potential prognostic factors was performed. After adjusting for the significant prognostic factors of performa...

An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck.

33 patients with locally and regionally advanced squamous cell carcinoma of the head and neck were treated with a single course of a combination of chemotherapy. Twenty-two of these patients were previously untreated, while the other eleven were previously treated with radiation therapy and/or surgery. Seventeen of the previously untreated patients had stage IV (M0) and the other 5 had stage III disease. Of the 33 patients; 26 received a three drug combination that consisted of: Cis-diamminedichloro-platinum II (DDP), Bleomycin (Bleo) and high dose Methotrexate (MTX) and leucovorin rescue. DDP was given on day 1; 100 mg/m2 with hydration and Lasix and Mannitol diuresis over 6 hours intravenously (iv). Bleo was administered as 15 units/m2 iv push on day 5 followed by 15 units/m2 a day for 5 days by continuous iv infusion. On day 10, the patient was evaluated and if there was no evidence of any toxicity, the patient was hydrated and alkalinated and MTX was given as 50 mg/m2 by rapid iv infusion followed by 1500 mg/m2 over 36 hours while maintaining the hydration and alkalinization. This was followed immediately by leucovorin; 25 mg/m2 iv over 15 minutes, then 200 mg/m2 over 12 hours iv. The patient then received leucovorin 25 mg/m2 intramuscularly (im) every 6 hours for 6 doses. The other 7 patients tolerated the first two drugs only, i.e., DDP and Bleo, and received no MTX because of decreased creatinine clearance. All patients were evaluated for response 2 weeks after the chemotherapy course, and prior to the local-regional therapy that consisted of surgery or radiotherapy. The response rates were 72.7% in previously untreated patients (16/22); with 4 complete responses (CR) and 12 partial responses (PR), and 54.5% in the previously treated group (6/11) all of them were PR. However, if we excluded three unevaluable patients that were considered failures from the study, the response rate in previously untreated patients would be 16/19 or 84.2%. The duration of response to such single course of chemotherapy was estimated to be 8–12 weeks. The toxicity in the 33 patients included vomiting in 18, alopecia, in 33, WBC below 2000 in 6, platelet count less than 50,000 in 6, mucositis in 7, and peak serum creatinine above 2 in 4 patients with two deaths. This combination chemotherapy seemed to be very effective in squamous cell carcinoma of the head and neck and could be applied prior to local-regional therapy. However, such program is still in experimental stages and should be carried out only in centers that have adequate facilities for close monitoring of the patients. Cancer 43:1025-1031, 1979.

Tariq Khan

Papers

Chemotherapy prior to local therapy in advanced squamous cell carcinoma of the head and neck: Preliminary assessment of an intensive drug regimen.