Raymond E. Lenhard

Therapy of malignant melanoma with an imidazole carboxamide and bis-chloroethyl nitrosourea

One hundred twelve evaluable patients with metastatic malignant melanoma were randomized to receive either a combination of DTIC 100 mg/m2/day × 5 days and BCNU 75 mg/m2/day × 2 days or DTIC 150 mg/m2/day × 5 days alone. The combination treatment yielded 12/61 responders as compared with 9/51 with DTIC alone. Responders survived significantly longer (7 months) than did nonresponders (3 months). Toxicity of both treatments was tolerable, but more frequent bone marrow suppression was encountered with DTIC‐BCNU combination. Patients were analyzed for relation between survival and the following: regional node dissection, length of the free interval, and positive urinary melanogens. Only the latter relation tended to be positive. We conclude that DTIC is the best agent for the therapy of melanoma with an expected response rate of 20%, and that its combination with BCNU does not add to its therapeutic effectiveness except in patients with central nervous system metastases.

CT scan modification in the treatment of mediastinal Hodgkin's disease

Seventy‐one patients with Hodgkins disease who were initially treated at Johns Hopkins with radiation or radiation‐chemotherapy from 1975–1980 had a five‐year cumulative disease‐free survival of I‐A—100% (12 patients); II‐A—85% (33 patients); II‐B—83% (seven patients); III‐A—75% (ten patients); and III‐B—66% (nine patients). Fifty patients with mediastinal masses at the time of treatment demonstrated no marginal misses, two mediastinal recurrences (96% local control), and three lung disseminations. CT scan data yielded stage and treatment modification in 60% (9/15) of recent patients with mediastinal Hodgkins disease. This demonstrates the need for routine thoracic scans and individual treatment planning in all mediastinal cases. Recommendations for combination treatment in early stage disease are made only for pericardial or extrathoracic chest wall extension based on CT scan findings, our low failure rates, radiation organ tolerances, and available relapse data in the literature, not arbitrary size designations from upright chest radiographs. It can be concluded that patients with mediastinal Hodgkins disease require CT scan analysis to identify unusual patterns of presentations, sites at risk, and to allow for proper application of radiation portals and/or chemotherapeutic management.

High-dose cyclophosphamide. An effective treatment for advanced refractory multiple myeloma

The Eastern Cooperative Oncology Group evaluated cyclophosphamide 600 mg/m2 intravenously daily × 4 (total dose each cycle 2400 mg/m2) as an aggressive approach to the treatment of patients with advanced multiple myeloma. The overall objective response rate is 43%. This includes a 38% response rate for all previously treated patients and a 29% response rate for patients refractory to prior therapy with cyclophosphamide. The objective response duration was 3 months and the survival of responding patients 9 months. A subjective response rate of 63% was observed, characterized by effective pain relief and improved performance. Sixty‐nine percent of patients experienced leukocyte cell nadirs < 500/mm2 with a mean time to marrow recovery of 17 days. Thrombocytopenia was less severe but required platelet transfusion in 43% of patients. Bone marrow toxicity was encountered in all patients, and death in aplasia is a significant risk. Strict adherence to entry criteria, and a systematic plan for hospitalization for antibiotic and blood component support is required for treatment with this regimen.

Eastern Cooperative Oncology Group experience with the rappaport classification of non-Hodgkin's lymphomas.

Eastern Cooperative Oncology Group experience in the cinical application of the Rappaport Classification of Non‐Hodgkins lymphomas (NHL) is reviewed in 670 cases studied since 1972. The diagnoses of institutional pathologists were reviewed by the Pathology Panel and Repository Center for Lymphoma Clinical Studies. Diagnostic agreement in regard to histologic pattern (nodular versus diffuse) was excellent (90%) but was less favorable when concurrence as to both pattern and cell type was assessed (82% in NLPD and 60% or less in other subtypes). Disagreement in regard to NHL diagnosis is related to the complexity of present nomenclature and to the lack of support of pathology activities within cooperative groups. It is suggested that patients entered into group NHL studies be randomized into favorable and unfavorable groups, primarily on the basis of histological pattern. Cancer 43:544–550, 1979.

Survival of nodular versus diffuse pattern lymphocytic poorly differentiated lymphoma

Response and survival were analyzed in 97 patients with NLPD (Nodular Lymphocytic Poorly Differentiated Lyphoma) and 77 with DLPD (Diffuse Lymphocytic Poorly Differentiated) treated by intensive versus moderate chemotherapy regimens. The complete and overall response rate in NLPD of 47% and 81% was significantly superior to 25% and 59% obtained in DLPD. The estimated two year survival of 83% in NLPD was also significantly superior to 47% two year survivorship of DLPD (p < .001). The chemotherapy responsiveness had a significantly favorable effect on DLPD survivorship with two year survivals of 84% for CR, 58% for PR and 17% for PD. In NLPD the effect of chemotherapy responsiveness on survival was less striking (CR 91%, PR 85%, and PD 72% surviving two years). The data, in our opinion, confirm the rationale for the use of aggressive multiple agent chemotherapy regimens in DLPD where achievement of complete response appears to be the single most important factor in improving survivorship. On the other hand NLPD, with excellent survival rates which appear to be only partially dependent on chemotherapy responsiveness might serve as an ideal model for moderate intensity or single agent chemotherapy trials.

Thoracic CT scanning for mediastinal Hodgkin's disease: results and therapeutic implications

Thoracic CT scans were performed on 42 newly diagnosed patients with Hodgkins disease. Five of 10 patients with negative chest X ray (CXR) had abnormal thoracic CT scans. Among the remaining 32 patients with mediastinal Hodgkins disease (MHD) on CXR, pericardial (Ep) and chest wall invasion (Ec) were the two most common sites of involvement which were detectable by CT scan alone. All 14 cases with Ep had M/T greater than or equal to 0.30 and 14 of 21 with M/T greater than or equal to 0.30 had Ep. Six cases had extensive Ec. Ep and Ec accounted for 16 of 19 of the changes in treatment portal or philosophy based on CT scan findings. Because of the high risk of cardiac or pulmonary radiation toxicity in Ep or Ec, radiation treatment alone may be inadequate. Treatment of mediastinal Hodgkins disease is reviewed here. The use of CT scans for identification of Ep, Ec, and other abnormalities will allow for more precise treatment, further define the use of conventional radiotherapy, combined modality therapy or whole lung irradiation, and allow more accurate analysis of treatment results.

Comparison of intensive versus moderate chemotherapy of lymphocytic lymphomas. A progress report

In an Eastern Cooperative Oncology Group trial, Cytoxan‐prednisone (CP) Induction was compared to BCNU‐prednisone (BP) in 273 patients with lymphocytic lymphoma. Response rates were comparable, with 21% achieving complete response and 40%, partial response. Patients with a nodular pattern responded better. Maintenance phase comparing cyclic intensive therapy (BCVP) with intermittent chlorambucil revealed the superiority of BCVP as demonstrated by improvement of the quality of response and somewhat longer remissions. The value of the Rappaport classification in the evaluation of lymphoma chemotherapy results is discussed. It is suggested that NHL be separated into “favorable” and “unfavorable” groups, based on the presence or absence of nodularity and treatment schedules devised accordingly.

Treatment of histiocytic and mixed lymphomas: a comparison of two, three and four drug chemotherapy.

The Eastern Cooperative Oncology Group has studied 187 patients with generalized progressive malignant lymphoma classified as having the histologic sub‐types histiocytic or mixed. Histology review by the Pathology Panel for Lymphoma Clinical Trials demonstrated a 31% disparity with contributing institutions pathologists in regard to cell type, but good agreement with interpretation of nodular or diffuse nodal pattern. Patients were assigned at random to treatment with cyclophosphamide 1 g/m2 on day 1 and prednisone 100 mg/m2 daily for five days (CP); CP plus vincristine 1 mg/m2 on day 1 (CVP); or CVP plus BCNU 60 mg/m2 on day 1 (BCVP). Chemotherapy was given for nine, twenty‐one day cycles. The observed complete remission rates were CP‐21%, CVP 34%, BCVP 34%. Both CVP and BCVP had significantly more complete remissions than CP, but survival following CVP (118 weeks) was significantly longer than that following either BCVP (76 weeks) or CP (74 weeks). Histologic sub‐type, lymph node pattern, response to chemotherapy, performance status and stage of disease were also found to influence survival.

Clinical Information System for Oncology

A Clinical Information System for Oncology describes a medical information system designed and implemented in a cancer center but with broad applicability to medical practice beyond the cancer center environment in both inpatient and outpatient settings. Regarded as forward looking in 1978, the system has the distinction of still being in production. Indeed, its functionality has continued to grow and its technical implementation to evolve with the changing technology over the last decade. The authors detail the functions supported by this unique system, illustrate how it assists in the care process, review its development history, and evaluate its impact on the delivery of care in terms of cost, user satisfaction, and efficacy. Unlike much information technology, the system is an active participant in medical decision making: it includes comprehensive tools for managing and displaying clinical data; automatically produces care plans from protocols; and features unique tools which support the effective use of blood products. Professionals in medical informatics, hospital administrators, and physicians will find this book a valuable addition to their professional library.

Combination chemotherapy of the malignant lymphomas. A Controlled clinical trial

The Eastern Cooperative Oncology Group has studied 113 patients with generalized progressive malignant lymphomas in a randomized clinical trial. Pathologic diagnosis was subclassified by cell type and nodal pattern by The Pathology Panel for Lymphoma Clinical Trials. Patients were randomly assigned treatment with either cyclophosphamide (C), vincristine (O), and prednisone (P) (COP) or CO without prednisone. Initial treatment was given for 8 weeks and further randomization of responders to observation or additional chemotherapy was carried out. A significant difference in complete remission rate between treatments was shown: with COP, 43%, and with CO, 17%, indicating an important role for prednisone in inducing CR. COP was also associated with longer remission durations and improved survival. Complete remission following initial chemotherapy is also associated with longer duration of disease‐free time and survival. The initial pathologic cell types and nodal pattern also strongly influence survival. Extended “maintainence” CO treatment improved disease‐free remission duration, but not survival.