nogalamycin and Pancreatic-Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Drug Evaluation; Female; Humans; Infusions, Intravenous; Male; Menogaril; Middle Aged; Nogalamycin; Pancreatic Neoplasms

High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult because contaminating stromal cells overgrow the malignant cells.. We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts.. Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified 77 U.S. Food and Drug Administration (FDA)-approved drugs with activity, and two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs.. Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Pancreatic Ductal; Cardiotonic Agents; Digitoxin; Female; Humans; Hypoxanthine Phosphoribosyltransferase; Interleukin Receptor Common gamma Subunit; Male; Mice; Mice, Nude; Mice, SCID; Nogalamycin; Ovarian Neoplasms; Pancreatic Neoplasms; Precision Medicine; Stromal Cells; Tumor Cells, Cultured

Fifteen patients with advanced adenocarcinoma of the pancreas were treated with menogarol 150-225 mg/m2 i.v. every 3 weeks. All patients had bidimensionally measurable disease. This regimen and dosage schedule are well tolerated, with minimal toxicity that included myelosupression; median white blood cell (WBC) count nadir of 2,700 cells/mm3 (range 1,400-7,100 cells/mm3) and median platelet nadir of 162,000 cells/mm3 (range 53,000-390,000 cells/mm3). Anorexia occurred in one patient, nausea or vomiting in six, phlebitis in one, and alopecia in six patients. No patients responded. At this dosage and schedule, there is no role for menogarol in the treatment of advanced pancreatic adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Daunorubicin; Drug Evaluation; Female; Humans; Male; Menogaril; Middle Aged; Nogalamycin; Pancreatic Neoplasms

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.

Topics: Adult; Aged; Alkaloids; Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Carcinoma, Intraductal, Noninfiltrating; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Female; Humans; Male; Menogaril; Mice; Mice, Nude; Microtubules; Neoplasm Transplantation; Nogalamycin; Paclitaxel; Pancreatic Neoplasms; Random Allocation; Transplantation, Heterologous