Twenty‐eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Gy) at 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5‐fluorouracil infusion 1000 mg/m2 on days 1–4 of the radiation therapy and repeated on days 29–32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4–6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty‐two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter at initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.

Induction chemotherapy, followed by surgery and/or radiotherapy was utilized in patients with advanced squamous cell carcinoma of the head and neck. During these trials, the authors observed that response to chemotherapy predicts further response to subsequent radiotherapy. This study was comprised of 57 patients with 60 separate neoplasms who demonstrated less than complete response (partial or no response) to initial treatment with a combination chemotherapy containing cisplatin. Subsequently radiotherapy, either 5000 rad preoperatively or 6600 rad as definitive therapy, was employed. Forty‐one of the 42 tumors with initial partial response to chemotherapy also responded to radiotherapy (97.6%). Only one of the 18 tumors that initially failed to respond to chemotherapy subsequently responded to radiotherapy (5.5%). This observation suggests that patients with head and neck cancer sensitive to initial chemotherapy share parameters that are also radiation sensitive.

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.

Twenty-one patients with squamous cell cancer of the esophagus were entered into a pilot clinical trial using preoperative chemotherapy (5-fluorouracil and cis-platinum) and radiation with the intent of improving cure rate and survival. After the preoperative treatment was complete, 15 patients (71%) were resected for cure. Seven (47%) of 15 had no histologic evidence of cancer in the resected esophagus, but two of these had microscopic cancer in resected lymph nodes. The median survival for all patients entered in the trial was 18 months, whereas for those with no cancer in the resected esophagus the median survival was 24 months. The six patients who either refused surgery (two patients) or were unresectable at surgery (four patients) died within nine months. Our conclusion in this trial is that survival and potential cure are clearly linked to successfully clearing the esophagus and nodes of histologic evidence of tumor through preoperative treatment.