Michael K. Samson

Dose-response and dose-survival advantage for high versus low-dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer a southwest oncology group study

One‐hundred fourteen patients with advanced testicular cancer were randomized to treatment consisting of either high‐dose (120 mg/m2, monthly) or low‐dose (15 mg/m2, daily X 5 monthly) cisplatin, both combined with vinblastine and bleomycin. There were 60 (53%) complete remissions and 42 partial remissions for an overall response rate of 90%. An additional 11 patients, 4 with carcinoma and 7 with mature teratoma, following surgical cytoreduction, were rendered free of disease. There was a significantly higher complete response rate for high dose induction chemotherapy, 63%, when compared with low dose, 43% (P = 0.03). A survival advantage was also observed for patients receiving high‐dose therapy (P = 0.009). For the subgroup of patients with maximal disease and embryonal ± teratoma ± seminoma histology there was a clear advantage in favor of high‐dose over low‐dose therapy both in complete response rate and survival (P = 0.03). There have been only four relapses, all occurring within 1 year of study entry. While there has been a higher frequency of leukopenia, renal, neuromuscular, and mucosal toxicity with high‐dose therapy, thus far no irreversable toxicity leading to functional impairment has been seen. The authors have demonstrated a clear‐cut relationship for dose of therapy, not only with response and survival, but with the increased potential for cure as well. Cancer 53:1029‐1035, 1984.

Vinblastine (VLB), bleomycin (BLEO), cis-diamminedichloroplatinum (DDP) in disseminated extragonadal germ cell tumors. A southwest oncology group study

Nineteen patients considered to have metastatic primary extragonadal germ cell cancer were entered on a Phase II chemotherapy study using as induction therapy a combination of vinblastine (VLB) 12 mg/m2 day 1, bleomycin (BLEO) 15 U/m2 I.V. or I.M. twice weekly, and cis‐diamminedichloroplatinum (DDP) 15 mg/m2 days 1–5, with vinblastine and DDP repeated at 28‐day intervals for four months. All complete or partial responders were then placed on a maintenance regimen of vinblastine 12 mg/m2 alternating monthly with actinomycin‐D 1.5 mg/m2 day 29, and chlorambucil, 10 mg/m2 P.O. days 32–37. There were three complete remissions (CRs), six partial remissions (PRs), and two stable disease. The response rate (CRs + PRs) was 56%; however, the mean duration of response was only two months (range, 1–8 months). Drug toxicity was significant and there was one toxic death. Unlike patients with disseminated testicular cancer, patients with primary metastatic extragonadal germ cell carcinoma appear to do less well on this particular drug regimen. Further investigation using different drug regimens seems necessary.

Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: A sarcoma intergroup study

In 1980, a consensus chemotherapy intergroup study for advanced malignant mesothelioma was initiated based on a collaborative agreement among the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Southeastern Cancer Study Group (SECSG). The purpose of the study was to evaluate cyclophosphamide (500 mg/m2 day 1), imidazole carboxamide (250 mg/m2 days 1 through 5), and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (50 mg/m2 day 1) v cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) in a randomized prospective clinical trial involving 76 fully evaluable patients with advanced stages II to IV malignant mesothelioma. A total of nine responses (12%) were documented, including three complete and six partial responses. There was no significant difference in response duration or survival between treatment arms. Leukopenia (greater than 2,000/microL) was observed in 46% of patients treated with the three-drug combination and 38% of patients receiving the two-drug combination. The variables of performance status 0-1 and the absence of prior chemotherapy/radiotherapy were significant with respect to favorable impact on survival. We conclude, based on the minimal benefit observed, that the combination of cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in patients with advanced-stage malignant mesothelioma.

Cisplatin.An active drug in the treatment of disseminated gastric cancer

Cis‐diamminedichloroplatinum (DDP) was administered at 100 mg/m2 intravenously bolus with every 3‐week schedule in patients with measurable and nonmeasurable incurable gastric cancer. Twenty patients were treated, 12 with measurable and 8 with nonmeasurable disease. Four of the 12 (33%) patients with measurable lesions had objective remissions. One remission was complete, lasting 60+ weeks. Patients with nonmeasurable disease were not eligible for response evaluation; they were followed for toxicity and survival. Hematologic, renal, and gastrointestinal toxicities were similar to those reported in other patient populations receiving DDP. Neurotoxicity proved to be dose limiting in two patients. The median survival was 38+ weeks for responders, 24 weeks for all patients, and 13 weeks for those 8 patients with nonmeasurable disease. DDP should be considered an active drug against gastric cancer. A better understanding of the dose response relationship for DDP in gastric cancer is necessary before the best dose and schedule can be chosen for DDP in combination with other active agents. Cancer 53:18‐22, 1984.

A PHENOTYPIC FEMALE WITH 49 CHROMOSOMES, PRESUMABLY XXXXX. A CASE REPORT.

A 2-year-old girl is presented whose cultured peripheral blood consistently hasprovided metaphase cells with 49 chromosomes. She is physically and behaviorally retarded and was born with patent ductus arteriosus which has been ligated. Minor stigmas of facies, irises, and extremities are described. On the basis of chromosome morphology, the presence of a significant number of buccal epithelial cells with 4 chromatin bodies, and the asynchronous segregation of 4 chromosomes in Group C as determined by uptake of tritiated thymidine, it is concluded that the extra chromosomes are of the X type. This aneuploid pattern has probably resulted from nondysjunction during both meiotic phases of ovular maturation and subsequent fertilization by an X-bearing sperm. It has been suggested that this be termed the penta X constitution pending description of other individuals with a similar chromosome pattern.

Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study.

The Southwest Oncology Group entered 453 patients with extensive small cell carcinoma into a combined modality treatment program, involving a randomized comparison of three different chemotherapy regimens for remission induction, and of maintenance chemotherapy alone versus maintenance treatment with cycles of reinduction added at six and 12 months. In addition, there was systematic comparison of diagnosis by institutional pathologist versus review panel pathologist. No difference was observed among the three different induction arms with respect to the incidence of response to treatment (61%), complete response (16%), or survival duration (median, 31 weeks). Neither overall response rate nor survival are superior to previous results. However, patients who achieved a complete response demonstrated significant survival benefit if they were in the group who received reinduction chemotherapy, as opposed to maintenance alone. This observation may apply most importantly to patients with small cell lung cancer of limited extent, for whom complete response is achieved in a majority. Agreement of institutional and review panel pathologists on the diagnosis of small cell lung cancer was observed in 94% of reviewed cases. A final observation is that the omission of chest irradiation results in a dramatic increase in the incidence of initial relapse at the primary tumor site. This suggests that future studies will need to use better therapy for local control in responding patients.

A phase II study of methyl CCNU in the treatment of solid tumors and lymphomas: A Southwest oncology group study

In March of 1972, the Southwest Oncology Group initiated a Phase II study, No. 7200, utilizing methyl‐CCNU in the treatment of patients with solid tumors and lymphomas. Initially, they received 200 mg/m2 orally as a single dose every 6 weeks. The dose was subsequently reduced in poor‐risk patients to 150 mg/m2. There were 69 responses noted in 675 evaluable patients (10%). The highest response rates were noted in patients with Hodgkins disease (13/31, 35%), malignant gliomas of the brain (8/29, 28%), anaplastic carcinomas of the lung (5/20, 25%), and squamous cell carcinomas of the head and neck (5/29, 17%). Squamous cell tumors appeared to be more responsive than adenocarcinomas (15% vs. 5%, respectively). Hematologic toxicity was cumulative, and was influenced by dose and prior treatment. There appeared to be no cross‐resistance in patients previously treated with alkylating agents. Methyl‐CCNU is an active antineoplastic agent. Further studies are indicated in order to determine relative effectiveness.

Vinblastine, bleomycin and Cis-diamminedichloroplatinum in disseminated testicular cancer: Response to treatment and prognostic correlations: A southwest oncology group study☆☆☆

Abstract One-hundred and forty-three patients with advanced germinal cell neoplasms of the testis were treated with a 4-month induction chemotherapy regimen of vinblastine, bleomycin and cis -diamminedichloroplatinum. Subsequent maintenance therapy for responding patients consisted of chlorambucil and actinomycin-D, alternating monthly with vinblastine. The duration of maintenance therapy was 20 months . Eighty-four patients ( 59% ) entered into complete remission while 34 patients ( 24% ) were partial responders. To date, 76% of patients in complete remission are relapse-free at 1 yr and 68% are relapse free at 2 yr . Significant leukopenia ( 3 ) was observed in over 50% of evaluable courses: thrombocytopenia ( 3 ) in 18% of courses. Major non-hematologic toxicities included renal, gastrointestinal, dermatologic and neuromuscular. Several prognostic factors were analyzed to determine the effect on complete remission rate, remission duration and survival. The most important parameters included histology, tumor burden, pre-treatment performance status and marrow reserve. Other important factors were pre-treatment level of HCG and LDH, histology and solitary site of metastatic disease. These factors should be incorporated in the design of future clinical trials.

Combination chemotherapy, radiotherapy, and BCG immunotherapy in limited small‐cell carcinoma of the lung: A Southwest Oncology group study

From November 1976 to March 1979 the Southwest Oncology Group treated 298 patients with limited (disease confined to the chest and encompassed by one radiotherapy port) small‐cell carcinoma of the lung with combination chemotherapy and radiotherapy with or without BCG immunotherapy. Two induction chemotherapy programs were utilized: (1) cyclophosphamide, vincristine, methotrexate, fluorouracil; or (2) cyclophosphamide, doxorubicin, and vincristine. Patients received 4500 rads of radiation therapy to the bulk primary tumor and 3000 rads to whole brain followed by maintenance chemotherapy. One‐half of all the patients were randomized to receive one vial (5 × 108) of high viability Pasteur BCG by scarification technique given on days 8 and 15 of each 21–28 day treatment cycle. Increased granulocytopenia accompanied the addition of BCG immunotherapy. Patients receiving BCG achieved a response rate of 49% vs. those patients not receiving BCG of 44% (P = 0.579). Median response duration was 40 weeks for the BCG arms and 38 weeks for the arms without BCG; survival was no different, 42 weeks for the BCG arms vs. 50 weeks for the arms without BCG. In patients who responded to therapy and survived longer than one year, those who continued to receive BCG therapy demonstrated a slight, yet significant, survival benefit over those patients not receiving BCG (93 weeks vs. 81 weeks, P = 0.03). It appears that BCG immunotherapy has no beneficial effect on response rate, duration of response, or survival in programs using chemotherapy and radiotherapy for control of limited small‐cell carcinoma of the lung except in this small group of long‐term survivors.

Acquired hypertrichosis lanuginosa. Report of two new cases and a review of the literature

Hypertrichosis lanuginosa is a pathologic state characterized by an excessive, new growth of fine, fetal hair. Two cases of hypertrichosis lanuginosa with malignancy (lymphoma and uterine cancer) are presented and added to the 9 in the literature. Lymphoma and uterine cancer are previously unreported as associated with hypertrichosis lanuginosa. Review of the 11 cases of hypertrichosis lanuginosa revealed the following characteristics: females were predominant; none was below the 4th decade; all had advanced neoplastic disease; all malignancies except one were of epithelial origin; and there were no demonstrable endocrine abnormalities. Despite an attempt to find etiologic factors in our patients and in the literature, none could be elicited.