Search for evidence of feline leukemia virus infection in humans with leukemias, lymphomas, or soft tissue sarcomas.

Two-hundred and thirty-nine patients, including 66 with soft tissue sarcomas and 173 with hematologic cancers, were investigated for evidence of infection with feline leukemia virus (FeLV). Included in this group were 2 patients with acute lymphocytic leukemia who had lived in the same household with leukemic cats. None of the patients demonstrated measurable levels of neutralizing antibody to FeLV or had detectable FeLV antigens in peripheral blood normal leukocytes or leukemic cells. In a smaller number of patients, there was no evidence of antibody to FOCMA or of FOCMA on tumor cells in the bone marrow.

Phase II trial of methyl-CCNU, vincristine, 5-fluorouracil, and streptozotocin (MOF-Strep) in patients with disseminated pancreatic carcinoma.

A phase II trial of methyl-CCNU, 5-fluorouracil (5-Fu), vincristine, and streptozotocin (MOF-Strep) was conducted on 20 patients with pancreatic carcinoma. There were two partial remissions (10%) lasting 3 and 10 months. In addition, there were two minor responses. The predominant toxicity was gastrointestinal, although hematologic and renal toxicity were also seen. Since the response rate to MOF-Strep does not appear to exceed that to 5-Fu alone, the usefulness of this combination in patients with pancreatic carcinoma is limited.

Phase II trial of methylglyoxal-bis-guanylhydrazone (methyl-GAG) in patients with soft-tissue sarcomas.

A phase II study of Methylglyoxal-bis-guanylhydrazone (Methyl-GAG) was conducted on 20 previously treated patients with soft-tissue sarcomas. No major responses were seen among 18 adequately treated patients. Toxicity including severe fatigue, muscle pains, and pharyngitis was noted in most patients. Methyl-GAG does not have significant antitumor activity in previously treated patients with soft-tissue sarcomas.

Tumor localization of the metabolically trapped radiolabeled substrates 2-deoxy-D-glucose and aminocyclopentanecarboxylic acid in human melanoma heterotransplants.

Analysis of the accumulation of metabolically trapped radiolabeled substrates in normal and malignant tissues may be useful for studying biochemical processes in vivo with positron emission tomography (PET). If labeled with the short-lived, positron-emitting radionuclide carbon-11 (T1/2 = 20.4 min), the glucose analog, 2-deoxy-D-glucose (2-DG), and the synthetic amino acid, aminocyclopentanecarboxylic acid (ACPC), may be useful for studying glucose utilization and amino acid transport in vivo. This study evaluated the biodistribution of the C-14 labeled analogues of these compounds in nude mice bearing human malignant melanoma heterotransplants. The data suggest that both 2-DG and ACPC accumulate in tumor tissue within 45 min.

Phase II evaluation of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) in patients with gastric adenocarcinoma.

A phase II study of m-AMSA in patients with gastric adenocarcinoma was conducted. Twenty-three patients received m-AMSA, 90-120 mg/m2, every 3 weeks. There were no major responses among 20 evaluable patients, although one patient experienced a minor response. Depression of the white blood count was the most prominent toxicity. m-AMSA has little activity in patients with gastric adenocarcinoma.

Evaluation of new anticancer agents against human pancreatic carcinomas in nude mice.

Heterotransplantation of human cancers in nude mice has provided an in vivo model for studying the biologic characteristics of human tumors, particularly their response to chemotherapy. In an effort to identify cytotoxic agents effective against pancreatic carcinoma, this model was used to evaluate the efficacy of three new anticancer agents--menogarol, 4'-epirubicin, and taxol--against two human transplanted pancreatic tumors. Relative area (tumor length X width) differed significantly between menogarol-treated and control groups (p = 0.034). A marked response was also observed in the tumors to 4'-epirubicin (p = 0.01). Taxol was ineffective in controlling tumor growth; by the fourth week, the size of treated tumors was similar to that of the control group (p = 0.55). No toxicity was observed in either the menogarol- or taxol-treated animals. Animals bearing the P2 tumor, and treated with 4' epirubicin displayed severe toxicity by day 18 with death by day 21 in most animals. For the second tumor, Capan-1, relative area differed significantly between the menogarol-treated and the control group (p = 0.003). In animals given 4'-epirubicin, a smaller difference was observed when comparing the relative areas (p = 0.09). Animals treated with taxol again showed no difference in the tumors when compared with controls (p = 1.0). The use of the nude mouse system has evolved so that tumor-oriented trials are now feasible with the hope of clinical applicability. This study illustrates that at least two agents--menogarol and 4'-epirubicin--may have some antitumor activity against pancreatic carcinoma in this system.

Etoposide (VP-16) in the treatment of advanced adenocarcinoma of the pancreas.

Twenty-six patients with advanced adenocarcinoma of the pancreas were treated with etoposide (VP-16), 100-180 mg/m2 i.v., days 1, 2, and 3, monthly. Twenty-five had bidimensionally measurable disease and one had evaluable disease only. This regimen and dosage schedule were well tolerated, with minimal toxicity including myelosuppression; a median WBC count nadir of 3,600 cells/mm3 (range 200-2,400); and a median platelet nadir of 215,000 cells/mm3 (range 15,000-405,000). However, no patients responded and only two had stable disease for 3.5 and 4 months, respectively. At this dosage and schedule, there is no role for VP-16 in the treatment of advanced pancreatic adenocarcinoma.

MIFA III (mitomycin-C, 5-fluorouracil, and adriamycin) chemotherapy for advanced adenocarcinoma of the pancreas.

Twenty-nine patients with advanced adenocarcinoma of the pancreas were treated with a combination of mitomycin-C, 5-fluorouracil, and adriamycin (MIFA III). Four of these patients achieved a partial response, and two achieved a minor response. An additional seven patients had evidence of disease stabilization. The median survival period from initiation of therapy for responders was 13.5 months as compared to 7.6 months for those with stable disease and 3.2 months for nonresponders (p = 0.001). Myelosuppression was the primary toxicity. Prolongation of survival was demonstrated in responding patients who had failed prior chemotherapy. The MIFA III regimen is active, well tolerated, and warrants further investigation in previously untreated patients.

Phase II evaluation of m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide) in patients with adenocarcinoma of the pancreas.

m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide, a substituted acridine derivative, was administered to 27 patients with adenocarcinoma of the pancreas. The dose ranged from 90-210 mg/m2/course. The toxic effects were primarily hematologic. Twenty-four of the patients were evaluable for response. These patients received a median of 2 doses (range 1-7). The median time from diagnosis to therapy was 2 months (range 0-16). Two patients achieved an MR lasting 4 and 2 months, respectively. Two patients had stabilization for 6 and 3 months. The median survival for all patients was 3 months. Survival distribution for patients with prior chemotherapy versus no previous therapy was not significantly different (p = 0.5). This study suggests that m-AMSA has little value as a single agent in the treatment of adenocarcinoma of the pancreas.

Scanning with L-(13 N) glutamate: Assessment of the response to chemotherapy of a patient with embryonal rhabdomyosarcoma.

The use of (13) N-labeled L-glutamate as an imaging agent in a patient with embryonal rhabdomyosarcoma is described. Localization of (13)N in a large, poorly defined tumor of the left pectoral region was seen, and clinically occult right axilliary metastases were also detected. A marked reduction in uptake in these areas occurred after chemotherapy, paralleling the clinical disappearance of tumor. These changes were verified on gallium scan. (13)N-labeled glutamate may be useful as an imaging agent, especially in patients with soft-tissue sarcomas.

Leiomyosarcomas of the extremities.

Leiomyosarcomas are uncommon malignant neoplasms that rarely arise in the extremities. We report on the clinical characteristics of 17 cases seen at the Memorial Sloan-Kettering Cancer Center over a 32 year period. Most neoplasms occurred in the lower extremities, and most of the tumors recurred after surgery alone, with several late recurrences. The overall prognosis was grim, with a median survival of 24 months. More aggressive multidisciplinary approaches to this disease are warranted.

Malignant mesothelioma in children: report of seven cases and review of the literature.

Seven children with malignant mesothelioma have been seen at Memorial Hospital since 1953. In six, the origin was at the pleura and in one at the peritoneum. None of the patients related a history of exposure to asbestos. Two patients lived more than five years. The other five patients died within two years of the diagnosis. Distant metastases were seen in four of the patients, including three who had metastases to brain. Surgery or radiotherapy were not effective in controlling the disease in most of the patients. One patient had a complete response to a combination of Adriamycin, cyclophosphamide, and vincristine and has remained free of disease for 5 1/2 years. The seven cases are reviewed, as are the other 42 cases of malignant mesothelioma in children reported in the literature.

Evaluation of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA, NSC 249992) on human tumors in nude mice.

The nude mouse human tumor-bearing system is a useful model for studying the efficacy of new drugs against human tumors. A panel of six selected human tumor heterotransplants was used to assess the activity of m-AMSA. No effect was seen against malignant schwannoma, malignant lymphoma, liposarcoma, neuroblastoma, or malignant melanoma. A testicular carcinoma appeared to respond to m-AMSA: however, statistical evaluation demonstrated that this was not significant. No evidence was found to support the use of m-AMSA as a sensitizing agent for radiation.

Effect of phase I and II chemotherapeutic agents against human lymphomas heterotransplanted in nude mice.

Ten chemotherapeutic agents, mostly phase I and II drugs, were tested for activity against two human lymphomas heterotransplanted in nude mice. Three of these agents have been tested in phase II trials in patients with lymphoma and found to lack activity; a corresponding lack of activity was found in lymphoma-bearing nude mice. Apart from cyclophosphamide, which is known to have activity against lymphoma and was used as a positive control, only dianhydrogalactitol (DAG) had antitumor activity in the lymphoma-bearing nude mice. Tumor regressions induced by DAG in a heterotransplanted diffuse histiocytic lymphoma were determined to be significant using a statistical method designed for such studies. These data suggest there should be further study of DAG in patients with lymphoma.

Basal cell carcinoma in black patients.

Fourteen cases of basal cell carcinoma occurring in North American black patients were reviewed. The majority of the lesions were asymptomatic, hyperpigmented, translucent nodules and were correctly diagnosed as being basal cell carcinomas prior to biopsy. All of the lesions except one arose in the sun-exposed areas of the head and neck, indicating that basal cell carcinoma in blacks, as in whites, is related to exposure to ultraviolet light. Microscopic examination revealed changes characteristic of basal cell carcinoma. The response to therapy in our patients was good. There appear to be no histologic or clinical differences in the basal cell carcinomas that arise in black and white patients.

Primary hemangiosarcoma of the spleen: report of four cases.

Four cases of primary splenic hemangiosarcoma are described. The most common presenting symptoms were recurrent, fever, malaise, and abdominal pain. Three patients also had complaints referable to the urinary tract. Severe hemolytic anemia with bizarre or fragmented red blood cells on peripheral smear was noted in three patients, in two cases, for more than 1 year before diagnosis. Two patients had been treated for mammary carcinoma with ionizing radiation 10 years before developing hemangiosarcoma of the spleen. One patient had multiple congenital hemangiomas present from birth, and is thought to have developed hemangiosarcoma in a previously existing benign hemangioma. None of our patients survived more than 7 months after the diagnosis of hemangiosarcoma. The importance of early detection and treatment of this tumor is discussed.

Chlorozotocin (DCNU)--induced pulmonary toxicity.

A case of pulmonary toxicity after chlorozotocin (DCNU) is described. This patient developed shortness of breath, nonproductive cough, and interstitial infiltrates after his third dose of DCNU. This was documented on pulmonary function tests which showed a reduction in vital capacity and pulmonary diffusion capacity. Similar findings have been reported in restrictive pulmonary disease associated with other nitrosoureas. This is the first case reported of pulmonary toxicity induced by DCNU.

Effect of desacetyl vinblastine amide (DVA) against human sarcomas heterotransplanted in nude mice.

The efficacy of desacetyl vinblastine amide (DVA) was tested against five human sarcomas heterotransplanted into nude mice. Marked antitumor effect was found against a lipoblastic liposarcoma, including complete regressions of tumor in some animals. A lesser, though statistically significant, antitumor effect was observed with a malignant schwannoma. No antitumor activity was seen against a leiomyosarcoma, epithelioid sarcoma, or Ewing's sarcoma. We conclude that DVA deserves study in the treatment of human patients with malignant sarcomas.

Lymphangiosarcoma after filarial infection.

A case of lymphangiosarcoma of a lower extremity is described in a patient with chronic lymphedema of that leg from a filarial infection in childhood. Histologically, the neoplasm resembled lymphangiosarcomas that arise in arms that become lymphedematous after mastectomies, but was different in that it also contained areas of calcification consistent with prior filarial infection. Calcifications were also present in muscle uninvolved by the lymphangiosarcoma of this case. The prolonged survival of this patient is unlike that of most patients with lymphangiosarcoma, which is generally shorter. Although lymphedema after filariasis is common, this is the first case of a lymphangiosarcoma arising in chronic lymphedema of filarial origin.