Jeannie Kinzie

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.

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.

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, IE, II, and IIE. 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.

Diffuse histiocytic lymphoma with sclerosis: A clinicopathologic entity frequently causing superior venacaval obstruction

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to mega‐voltage radiotherapy alone and relatively resistant to combination chemotherapy.

Non-hodgkin's lymphoma, poorly differentiated lymphocytic and mixed cell types. Results of sequential staging procedures, response to therapy, and survival of 100 patients

The results of sequential staging procedures including laparotomy, radiotherapy, and combination chemotherapy are reported for 100 patients with poorly differentiated lymphocytic (PDL) and mixed cell (MC) non‐Hodgkins lymphoma (NHL). Twelve patients were found to have localized disease, pathologic stage (PS) I or II; 88 patients had PS III or IV disease. Bone marrow biopsy showed a high incidence of involvement and advanced 34% of the patients from CS I, II, and III to PS IV. Staging laparotomy has a very limited role in the evaluation of these patients. All of 12 patients with PS I and II NHL were treated with radiotherapy; at 5 years, they had 100% survival, 80% being disease‐free. Fifteen patients with PS III disease were treated with total nodal radiotherapy (TNRT) alone and had a median disease‐free survival of 41 months. The remaining patients with PS III and IV disease were treated with chemotherapy consisting of vincristine and prednisone (V & P); cyclophosphamide, vincristine (Oncovin®), procarbazine, and prednisorte (COPP); cyclophosphamide, vincristine (Oncovin®), adriamycin, and prednisone (COPA); or “palliative therapy”, consisting of chlorambucil and prednisone. Two‐year and 4‐year survivals for patients with diffuse lymphoma were 93% and 60%, respectively; for patients with +2 nodular lymphoma, 80% and 30%; for patients with nodular lymphomas, 76–93% and 50%, respectively. Treatment with COPP showed no advantage over V and P, “palliative therapy,” or TNRT for patients with +2 nodular and nodular disease. The likelihood of cure appears most promising for patients in complete remission (CR) with diffuse lymphoma; patients in CR with nodular lymphoma show a high rate of relapse over 5 years of observation. We conclude that staging laparotomy in PDL and MC NHL is of limited value, and that the role of aggressive chemotherapy for patients with +2 nodular and nodular lymphoma needs to be redefined.

Pathologic stage I and II Hodgkin's disease, 1968‐1975. Relapses and results of retreatment

Sixty‐seven previously untreated patients with Hodgkins disease, pathologic stages I and II, seen during a 7‐year period were evaluated 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.