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Biomedical subjects

J Kinzie

Publications and source records attributed to J Kinzie.

36 records · Page 2Linked to original sources

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.

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.

Adolescent↗

Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck.

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.

Antineoplastic Combined Chemotherapy Protocols↗

Superior clinical response and survival rates with initial bolus of cisplatin and 120 hour infusion of 5-fluorouracil before definitive therapy for locally advanced head and neck cancer.

One hundred ninety-one patients were treated by one of three cisplatin-containing multidrug protocols. The initial 77 patients received two courses of cisplatin and vincristine plus bleomycin. The next 26 patients received two courses of 5-fluorouracil and cisplatin, and the final 88 patients were placed on a three course 5-fluorouracil and cisplatin protocol. Overall response rates were similar for each of the three protocols. The complete response rate, however, was much better (54 percent) for three course 5-fluorouracil and cisplatin versus cisplatin vincristine, and bleomycin (29 percent) and two course 5-fluorouracil and cisplatin (19 percent). Survival curves were also better for the three course 5-fluorouracil and cisplatin segment of this nonrandomized pilot study.

Adolescent↗

Preoperative chemotherapy and radiation therapy for patients with cancer of the esophagus: a potentially curative approach.

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.

Adult↗

Adjuvant chemotherapy with cis-diamminodichloroplatinum II and 120-hour infusion 5-fluorouracil in Stage III and IV squamous cell carcinoma of the head and neck.

A prospective study was carried out to investigate the effectiveness and toxicity of three courses of combination high-dose bolus CDDP and 120-hour continuous infusion 5-FU every three weeks prior to definitive surgery and/or radiation therapy in 35 patients with locally advanced Stage III and IV squamous cell carcinoma of the head and neck. Twenty-two patients (63%) achieved a CR and 11 (31%) a PR after three cycles of chemotherapy, for an objective response rate of 94%. Toxicity was clinically acceptable. Nausea and vomiting occurred in 23 of 35 (66%) without any patients discontinuing therapy for this reason. Leukopenia in 13 (37%) and reversible azotemia in six (17%). Following three courses of chemotherapy, 13 patients had surgical resection and 12 patients had radiation therapy. Ten of these 35 patients had no pathologic evidence of cancer in the surgical specimen or preradiation therapy biopsy. Only two patients of those achieving a complete objective response have relapsed. However, the median follow-up has been short. The authors concluded that three courses of CDDP and 5-FU is a highly effective and safe adjuvant treatment in patients with advanced carcinoma of the head and neck.

Carcinoma, Squamous Cell↗

Management of malignant bronchoesophageal fistulas.

Twenty-four patients with a bronchoesophageal fistula due to a malignant lesion were seen during the eight years from 1974 to 1981. Twenty of the patients had carcinoma of the esophagus, and four patients had carcinoma of the lung. All three patients who had a Celestin tube inserted had gastric reflux, and in two, the fistula was not completely occluded. Four patients who had a cervical esophagostomy, feeding jejunostomy and ligation of the gastroesophageal junction died in the immediate postoperative period. The best palliative result was achieved in 17 patients who had a bypass of the fistula with the stomach. Fourteen had a substernal gastric bypass to the cervical portion of the esophagus, and three patients had a gastric bypass to the upper thoracic portion of the esophagus by way of a right thoracotomy. Although the operative deaths occurred in six of 17 patients, the surviving patients resumed oral feeding within ten to 14 days after operation, and the pneumonias cleared. These patients had, by far, the best palliative result. We, therefore, advocate substernal or intrathoracic bypass of the bronchoesophageal fistula as soon as the general condition of the patient permits.

Adult↗

Clinical trial of cisplatin and 5-FU infusion as initial treatment for advanced squamous cell carcinoma of the head and neck.

Initial treatment with drug combinations that include cisplatin and bleomycin has been effective in reducing tumor in patients with previously untreated epidermoid cancers of the head and neck. Because of the threat of pulmonary complications from bleomycin, patients with poor pulmonary function were excluded from those studies. We conducted a trial using the combination of cisplatin (100 mg/m2) and a 96-hour infusion of 5-FU (1000 mg/m2/day) and achieved a response rate of 88.5% in 26 patients treated with two courses. Five of these patients had complete remissions and 18 had partial remissions. Nausea and vomiting (experienced by 70% of the patients) was the predominant toxic effect, and 26% experienced leukopenia. Although all patients were initially inoperable, six underwent resection following chemotherapy, and another six underwent resection after chemotherapy and irradiation. Two additional patients were treated with radiation therapy after clinically achieving complete remissions following chemotherapy, and another ten received X-ray therapy after chemotherapy. Cisplatin and 5-FU infusion are effective without being as toxic as bleomycin in patients with previously untreated advanced carcinoma of the head and neck.

Adult↗

Survival of patients with localized diffuse histiocytic lymphoma.

Twenty-eight patients with previously untreated diffuse histiocytic lymphoma (DHL) were identified to be in pathologic stage (PS) I (11), IE (3), II (8), or IIE (6) by exploratory laparotomy and splenectomy. Six patients were treated with total nodal radiotherapy; 14 with an extended mantle; 5 with an inverted Y or whole abdomen; and 3 with an involved field. Twenty-six patients achieved a complete remission (93%) and 2 patients had persistent local disease. The median survival and disease-free survival and for the complete response group are 56 and 51.5 mo, respectively. Ten of the 11 stage I or IE patients had supradiaphragmatic lymph node disease. Patients with stage I or IE disease (n = 14) demonstrated a median survival of 72.5 mo and a median disease-free survival of 69.5 mo; there was 1 disease-related death. Patients with stage II or IIE disease (n = 14) demonstrated a median survival of 33 mo and median disease-free survival of 29.5 mo; there were 10 relapses or deaths. Patients in stages I, IE, II, or IIE with infradiaphragmatic disease (n = 7) had a median survival of 36 mo, while patients with supradiaphragmatic presentation (n = 21) demonstrated median survival of 68 mo (p = 0.37). The data indicate that patients with diffuse histiocytic lymphoma with stage I supradiaphragmatic lymph node disease are curable using radiotherapy alone, achieving a 93% 11-yr actuarial disease-free survival. Patients with stage II or IIE diseases are not readily curable with radiation therapy alone, achieving a 33% 11-yr actuarial disease-free survival; radiotherapy with adjuvant chemotherapy or chemotherapy alone should be considered for this group.

Actuarial Analysis↗

Pathologic stage I and II Hodgkin's disease, 1968--1975: relapse and results of retreatment.

Sixty-seven previously untreated patients with Hodgkin's disease, pathologic stages I and II, seen during a 7-year period were evaluted with respect to initial staging and treatment, as well as relapse and retreatment results. The initial treatment consisted of radiation therapy (RT) to an involved field (IF) or an extended field (EF) for patients with stages IA and IIA, or RT and, in recent cases, combination chemotherapy [cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP)] for patients with stages IB and IIB. Nineteen of the 67 patients relapsed (28%), including 11 of 56 patients with stages IA and IIA (20%) and 8 of 11 patients with stages IB and IIB (73%). Seventeen of the 19 relapses occurred within 24 months after completion of the initial therapy (89%). The relapse-free survival at 5 years was 75% for the A patients and 25% for the B patients. The actuarial survival of stage IA and stage IIA patients at 5 years was 91%; there was no significant difference between patients treated initially with either IF or EF. The actuarial survival at 5 years for the patients with stages IB and IIB was 88%, as most responded to a second program of induction therapy. No correlation could be found between the pattern of relapse and the initial pathologic stage or the mode of treatment.

Adolescent↗

Survival of patients with localized histiocytic lymphoma.

Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, I(E), II, II(E). Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved-field radiotherapy. The survival rate and relapse-free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.

Adolescent↗

Consequences of radiotherapy and antineoplastic therapy for the fetus.

The consequences of radiation and antineoplastic therapy on the fetus are summarized. Animal and atom bomb studies clearly demonstrate the carcinogenic effects of radiation. Less information is available on neoplasia and neonatal malformations induced by chemotherapy, but there may be an increased risk. The delayed consequences of radiation and chemotherapy are not well known and require further study.

Abnormalities, Drug-Induced↗

Noncytokinetic radiation injury: anticoagulants as radioprotective agents in experimental radiation hepatitis.

Rats that have been irradiated with a single dose of 1500 roentgens directed to the liver show the following abnormalities: increased clearance of colloidal gold by the liver at 30 days, a decreased albumin space index at 30 days, and increased alkaline phosphatase at 60 days. In each of these cases, animals receiving Depo-heparin in dose ranges reasonable for human application had essentially normal values. There was no radioprotective effect with salicylates at the doses used. Higher doses of salicylates resulted in death of the animals.

Albumins↗

cis-platinum and 5-fluorouracil as initial therapy in advanced epidermoid cancers of the head and neck.

A total of 44 patients with previously untreated Stage IV squamous cell carcinomas of the head and neck were treated with a combination of cis-platinum (100 mg/sq m) and 96-hour infusion of 5-fluorouracil (5-FU) (1,000 mg/sq m/day) in two courses or with cis-platinum (100 mg/sq m) and 120-hour infusion of 5-FU (1,000 mg/sq m/day) in three courses. In the 26 patients receiving the two course regimen, the tumor response rate was 88.5%. In five of the 26 patients complete disappearance of the tumor was achieved; partial remission was obtained in 18 of 26 patients. The main side effects were nausea and vomiting (70%), leukopenia (27%), and mild-to-moderate renal toxicity (27%). In the 18 patients who received the three course regimen of 5-FU and cis-platinum, there were 11 (61%) complete responses, 6 (33%) partial responses, and 1 (6%) minimal response. The incidence of complete response was increased with each course given. No added toxicity was observed with surgery or radiotherapy.

Adult↗