Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer.

AIMS: Currently available therapies do improve survival in advanced stage non-small cell lung cancer (NSCLC), but only to a limited degree. Talabostat mesilate (PT-100) is an orally available amino boronic dipeptide that specifically inhibits dipeptidyl peptidases (including fibroblast activation protein) and enhances an immune response. The aim of this study was to determine the efficacy and safety of talabostat in NSCLC patients. MATERIALS AND METHODS: A phase II trial was conducted to evaluate talabostat in combination with docetaxel in patients with advanced NSCLC after failure of previous platinum-based chemotherapy. In total, 42 patients were enrolled. RESULTS: Talabostat was well tolerated. Two patients achieved a partial response and one achieved a complete response. CONCLUSION: There was no evidence that talabostat enhanced the clinical activity of docetaxel in patients with NSCLC.

ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study.

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.

Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome.

A patient with a pleomorphic intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presented clinically with a superior vena cava syndrome. A latent period of 29 years elapsed between receiving orthovoltage radiation to the neck and right side of chest to treat recurrent ganglioneuroblastoma, and the appearance of a leiomyosarcoma and subsequent recurrences. The patient underwent partial resection of the tumor, received adjunct chemotherapy, and was shown to be free of disease by clinical tests and by magnetic resonance imaging (MRI) 17 months after completion of chemotherapy. The criteria for the diagnosis of radiation-induced sarcomas are reviewed in relation to the present case. The critical role of magnetic resonance imaging in both the diagnosis and continued follow-up of the patient is described. This would appear to be the first reported case of radiation-induced intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presenting as a superior vena cava syndrome.

Pseudo-Gaucher cells in the bone marrow of a patient with Hodgkin's disease.

The authors studied an 18-year-old woman with stage IIIB nodular sclerosis Hodgkin's disease whose bone marrow contained abnormal storage cells that resembled Gaucher cells by light microscopic examination ("pseudo-Gaucher" cells). Electron microscopic examination revealed that these cells differed from true Gaucher cells and resembled storage cells previously described in chronic myelogenous leukemia. The patient's peripheral blood leukocyte beta-glucosidase and serum acid phosphatase levels were elevated, ruling out the diagnosis of inherited Gaucher's disease. After treatment with six monthly cycles of systemic chemotherapy (nitrogen mustard, vincristine, procarbazine, bleomycin, doxorubicin, and prednisone), all signs of Hodgkin's disease and pseudo-Gaucher cells disappeared. Repeat leukocyte beta-glucosidase and serum acid phosphatase levels were unchanged. The present case is unique with its documentation of classical enzyme patterns for beta-glucosidase and acid phosphatase and electron microscopic features. The authors postulate that pseudo-Gaucher cells result from excessive cell breakdown with an overload of available beta-glucosidase.

Treatment of six cases of mesothelioma with doxorubicin and cisplatin.

Six patients with unresectable malignant mesothelioma were treated with chemotherapy consisting of doxorubicin and cisplatin every 3 weeks. One patient with paratesticular mesothelioma metastatic to lungs entered complete remission for 8 months; his disease has relapsed but he is alive 32 months after initiation of chemotherapy. One patient with peritoneal mesothelioma achieved partial response for 12 months. Two patients with pleural mesothelioma achieved a partial response of 5- and 6-month durations, respectively. Two patients with pleural mesothelioma failed to respond to this regimen. Thus, four of six patients responded to doxorubicin-cisplatin chemotherapy. These preliminary results merit further study and confirmation; future investigations of cisplatin alone are necessary to better define the role of this agent in mesothelioma.

Lactic acidosis in lung cancer.

Because the liver is the dominant site of lactate clearance and utilization, extensive liver metastases may predispose the patient to the development of lactic acidosis. We have described two patients with hepatic metastatic disease who had fatal lactic acidosis. Greater awareness and prompt treatment of this frequently fatal complication may improve survival of patients with potentially treatable advanced malignancies.

Chemoendocrine therapy vs chemotherapy alone for advanced breast cancer in postmenopausal women: preliminary report of a randomized study.

From January 1980 to August 1982 the Cancer and Leukemia Group B conducted a prospective randomized trial comparing chemoendocrine therapy with T-CAF (cyclophosphamide, adriamycin, and 5-fluorouracil plus tamoxifen) to CAF alone in postmenopausal women with advanced breast cancer. The patients were stratified by estrogen receptor (ER) status into three groups: ER-negative, ER-positive, ER-unknown. They were also stratified by dominant site of metastatic disease: visceral and other (osseous and/or soft tissue). A total of 246 eligible patients were enrolled in the study; 232 were evaluable and constitute the basis for this report. The study revealed that there was no difference in overall response frequency or response duration between T-CAF and CAF; there was no difference in response between T-CAF and CAF in ER-positive or in ER-negative patients; and there was no difference in response between T-CAF and CAF by dominant site of metastatic disease. The expected advantage of T-CAF over CAF, especially for ER-positive patients, was not observed.

Pleural effusion in breast carcinoma: analysis of 122 cases.

One-hundred-twenty-two patients with breast carcinoma and pleural effusion were analyzed for the laterality of effusion and survival. Ipsilateral effusion occurred in 83% of the patients. The median survival of these patients was six months after the onset of effusion. Systemic therapy is recommended even in the absence of other evidence of metastases.