Melvin L. Samuels

Survival with inoperable lung cancer. An integration of prognostic variables based on simple clinical criteria

The objectives are to identify and integrate through regression analysis those fundamental clinical variables predicting survival of patients with inoperable lung cancer managed in a modern setting. Median survival time from first treatment in 129 patients with limited disease and 187 patients with extensive disease was 36 and 14 weeks, respectively. Within the proposed survival model for limited disease, weight loss was the major prognosticator followed by symptom status, supraclavicular metastases, and age. Within extensive disease, symptom status and age were dominant variables followed by weight loss and metastases to liver, opposite hemithorax, brain, and bone. Survival by cell type was similar within the limited and extensive disease groups. The data identify the essential factors which must be controlled or accounted for in studies analyzing survival as a dependent variable.

Bleomycin combination chemotherapy in the management of testicular neoplasia.

Eighty‐three patients with Stage II or Stage III germinal neoplasia of the testis and 7 patients with extragonadal primary tumors were treated with bleomycin plus vinblastine, or a five‐drug program, bleomycin plus cyclophosphamide, vincristine, methotrexate, and 5‐fluorouracil. Of the 70 Stage III patients, there were 53 responses (75%), 22 complete and 31 partial. The mean survival of the complete responders is 100+ weeks, with 3 dead. The mean survival of the partial responders and nonresponders is 38 weeks and 33 weeks, respectively. There is a highly significant difference between complete responders vs. partial and nonresponders (p < 0.01). Thirteen patients with nonmeasurable disease (Stage II and Stage III postresectional status) but at great risk to develop widespread metastasis were treated prophylactically after conventional therapy. Nine continue in complete response to 36 months. The 7 extragonadal primary patients showed 4 partial responses, none complete. Major toxicity was myelosuppression and also bleomycin pneumonitis in 5 of the 90 evaluable patients.

Metastases from testicular carcinoma Study of 78 autopsied cases

The necropsy records of 78 patients with histologically proved germ cell tumors of the testis, who died as a direct result of their malignant disease, were reviewed to determine the usual modes of spread, distribution of metastasis, the histologic characteristics of the metastatic foci as compared with the morphology of the primary tumor and the specific cause of death. The sites of metastases in order of decreasing frequency for all cases were lung, retroperitoneal lymph nodes, liver, mediastinal lymph nodes, brain, kidney, gastrointestinal tract, bones, adrenals, peritoneum and spleen. The absence of metastases solely in the anterior mediastinum without involvement of other mediastinal nodes (middle/posterior) strongly supports the premise for a primary extragonadal origin whenever the anterior mediastinum alone is involved with malignant disease having the histologic appearance of a primary germ cell tumor. The histologic features of the metastatic lesions were usually similar in nature to those of the primary tumor except for seminoma in which the metastatic lesions proved to be of a different histologic pattern in almost one third of the patients dying from the disease. It should be axiomatic that whenever a patient with seminoma fails to respond appropriately to radiotherapy that his treatment be immediately discontinued and that appropriate biopsies be obtained to substantiate the histologic pattern present.

Is Nephrectomy Justified in Patients with Metastatic Renal Carcinoma

The survival data of 93 patients with metastatic renal carcinoma are discussed with respect to the site of metastasis and whether nephrectomy was performed as part of the initial treatment. Analysis of the cumulative survival rates revealed that nephrectomy significantly increased survival only for those patients pesenting exclusively with osseous metastases. Nephrectomy did not alter survival for patients with pulmonary and/or soft tissue metastases.

High‐dose combination chemotherapy with autologous bone marrow transplantation in adult solid tumors

In order to determine whether high‐dose combination chemotherapy was active in chemotherapy resistant patients, 19 patients, (9 with small cell bronchogenic carcinoma, 6 with embryonal cell carcinoma, 2 with diffuse histiocytic lymphoma, 1 with Hodgkins disease and 1 with chondrosarcoma), 18 of whom had had extensive prior chemotherapy and failed, received 23 courses of high‐dose chemotherapy with autologous bone marrow infusion (ABMT). Three patients received four courses of cytoxan (2–6 g/m2) and VP‐16 (500–600 mg/m2) and 16 patients received 19 courses of cytoxan and VP‐16 in these doses plus BCNU (300 mg/m2). Activity was observed in 6 of 8 evaluable small cell bronchogenic carcinoma patients (1 complete response (CR), 4 partial responses (PR), 1 < PR), in 6 embryonal cell carcinoma patients (3 CR, 2 PR, 1 < PR), in both patients with diffuse histiocytic lymphoma (1 CR, 1 < PR), in the patient with Hodgkins disease (1 PR); and in the patient with chondrosarcoma (stable). Only 2 patients who had received prior cytoxan and VP‐16 extensively showed resistance to these programs. The median response duration was 11 weeks (range = 4–55+ weeks). Major toxicity consisted of bacterial infections. Two patients died from treatment related causes. Neutrophils recovered to levels of ⩾ 1.5 × 109/liter by days 20–42 (median, day 27) and platelets to levels of ⩾ 100 × 109/liter by days 21–56 (median, day 32) without any delayed BCNU toxicity. High‐dose combination chemotherapy with ABMT causes acceptable toxicity and high response rates of relatively short duration in tumors refractory to conventional chemotherapy.

Localized ewing's sarcoma—treatment and results

The experience at M. D. Anderson Hospital in the management of 59 patients with apparently localized Ewings sarcoma from 1948 to May, 1972 is presented. Necropsy examination was performed in 18 cases. Disease‐free survival times are compared between 19 patients treated by the combination of high‐dose irradiation and intensive chemotherapy, and 40 patients treated by radiation therapy alone (25) or in combination with relatively less intensive drug therapy (15). Results favor the former group: local recurrence in 1 case of 19 compared to 19 of 40; and median time to first metastasis of >15 months compared to 8 months.

Management and results of localized Ewing's sarcoma.

Seventy‐six patients with localized Ewings sarcoma who received primary treatment at M. D. Anderson Hospital from 1948 through December 1975 were reviewed. Patients have been divided into four groups according to the different treatment regimens they received: Group I, moderate dose radiotherapy alone; Group II, high dose radiotherapy alone; Group III, radiotherapy plus vincristine and cytoxan; and Group IV, radiotherapy plus vincristine, Adriamycin, cytoxan and actinomycin. The problem of local recurrence appears to be solved with combined chemotherapy and radiation therapy with only one of 36 patients having a recurrence at the primary site in Groups III and IV. Multimodal therapy is the preferred treatment to obtain control of the primary lesion by radiation therapy while preserving good function. However, the major cause of failure remains distant metastases, 19 of 36 (53%) in Groups III and IV. In addition, 4 of 10 patients who have survived over 5 years have developed osteogenic sarcoma. Cancer 43:1001–1006, 1979.

The treatment of advanced testicular carcinoma with high dose chemotherapy and autologous marrow support

Abstract Thirteen patients with disseminated nonseminomatous germ cell carcinoma, failing to respond to extensive prior chemotherapy including cis -platinum, were treated with high dose chemotherapy. Cyclophosphamide (4.5g/m 2 ) and epipodophyllotoxin (VP-16) (600 mg/m 2 ) were given followed by autologous bone marrow transplantation. In some cases 1,3 bis (β-chloroethyl)- 1 -nitrosourea (BCNU), adriamycin or platinum were also administered. Of 10 patients evaluable for response 9 responded; 4 patients achieved a complete remission and 3 a partial remission. Median response duration was 15 weeks (range 4 to 20+ weeks ). Four patients died from treatment-related infections; 2 of whom entered the program already with fever and 3 of whom died after hematopoietic recovery. Major toxicities were bacterial and fungal infections. In patients treated with cyclophosphamide and VP- 16 only, no fever was seen in 3 out of 9 courses. Granulocyte transfusion was given in only 1 of 9 courses. Neutrophils recovered to greater than 1.5 × 10 9 /liter by day 18–35 (median 23 ) and platelets greater than 100 × 10 9 /liter by day 16 to 42+ (median 21 ). Further experience with high dose cyclophosphamide and VP- 16 followed by autologous bone marrow transplantation is needed to evaluate its value in the management of patients with disseminated nonseminomatous germ cell tumor failing front line conventional chemotherapy.

Transcatheter intraarterial infusion of chemotherapy in advanced bladder cancer

Bilateral internal iliac artery infusion of chemotherapeutic agents in patients with advanced bladder carcinoma, Stage D, resulted in a 50% response or greater in nine of 15 patients with a median survival, thus far, of 52 weeks. Hematuria was controlled in eight of ten patients, and pain was relieved in 12 of 15 patients. Three additional patients were treated as adjuvants after their residual tumor was removed surgically or irradiated before chemotherapy. Cis‐diamminedichloroplatinum (CDDP) was infused at a dose of 80–120 mg/m2 over a 24‐hour period. When CDDP failed or in the presence of impaired renal function, a combination of 5‐fluorouracil (5‐FU) infused intraarterially while Adriamycin and mitomycin C were delivered intravenously, salvaged two patients. Complications were tolerable, consisting of transient acute tubular necrosis in two patients, a lower extremity embolus in one, and skin reactions due to 5‐FU in two patients.

Split-course irradiation compared to split-course irradiation plus hydroxyurea in inoperable bronchogenic carcinoma--a randomized study of 53 patients.

Fifty‐three patients with inoperable but regionally localized non‐oat cell bronchogenic carcinoma were evaluated in a prospective randomized study of the use of split‐course irradiation alone and split‐course irradiation used in conjunction with hydroxyurea. The 25 patients receiving irradiation alone had 1‐ and 2‐year absolute survivals of 48% and 12% respectively, whereas the 28 patients receiving irradiation plus hydroxyurea had 46% 1‐year and 11% 2‐year survivals. Survival in the split‐course irradiation group was comparable at 2 years to that in a previous, similar group of patients irradiated continuously, but slightly inferior in terms of long‐term survivors. The split‐course rest period affords important patient observation time, permitting the elimination of unnecessary further irradiation in those patients who develop early distant metastases.