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D Von Hoff

Publications and source records attributed to D Von Hoff.

29 records · Page 2Linked to original sources
PubMed1991

A phase I trial of taxol given by a 6-hour intravenous infusion.

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.

Alkaloids↗
PubMed1985

Eastern Cooperative Oncology Group phase II studies in advanced measurable colorectal cancer. I. Razoxane, Yoshi-864, piperazinedione, and lomustine.

During a 6-month interval, Eastern Cooperative Oncology Group randomized 127 patients who had received prior chemotherapy, and who had advanced measurable, surgically incurable colorectal cancer, to receive piperazinedione (PZD), Yoshi-864, or razoxane (ICRF-159). The observed response (and median survival) rates were: PZD, one of 35 patients (17 weeks); Yoshi-864, one of 34 (19 weeks), and ICRF-159, none of 38 (23 weeks). Among 107 evaluable patients, there were five episodes of life-threatening toxicity with PZD (one death) and four with ICRF-159 (two deaths). In the same protocol, 42 evaluable patients who had not received prior chemotherapy were randomized to be treated with lomustine (CCNU) or one of the three drugs in the "previously treated" trial. One CR (41 weeks) was seen with ICRF-159 and two PRs were seen with CCNU. Life-threatening toxicity occurred in three patients, two who received CCNU (one death) and one who received PZD. No survival advantage was seen. We do not encourage further phase II trials in colorectal cancer with the agents studied.

Antibiotics, Antineoplastic↗
PubMed1980

A phase II study of neocarzinostatin (NSC 157365) in malignant hepatoma. An Eastern Cooperative Oncology Group pilot study.

Thirty evaluable patients with histologically confirmed primary liver cancer (PLC) were treated with neocarzinostatin (NCS). All patients had measurable disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, or 3. NCS 2250 units/m2 was given daily for 5 days, repeated at 28-day intervals. Hemopoietic suppression was the major side effect. In 23 of 30 patients (13 with leukopenia and 19 with thrombocytopenia), this toxic effect was documented. Other toxic effects included nausea, vomiting, allergic-type reaction, and elevation of NPN. Partial response, with a median duration of 12.7 weeks (range 4--37 weeks) was observed in seven patients. In nine patients the response was classified as no change, and in 14 patients there was progressive disease. NCS has some therapeutic activity in patients with PLC.

Adult↗
PubMedDate not supplied

MGI 114: augmentation of antitumor activity when combined with topotecan.

PURPOSE: 6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic analogue of the mushroom toxin illudin S that has been shown to be a potent cytotoxic agent with an improved therapeutic index compared with its parent compound. The studies were conducted to evaluate the antitumor activity of MGI 114 as a single agent and in combination with topotecan against pediatric solid tumor cell lines and xenograft models. MATERIALS AND METHODS: In vitro studies were designed to determine the cytotoxic potential of MGI 114 using the MTT assay and 13 pediatric tumor cell lines. In addition, combination in vitro studies were performed with MGI 114 and topotecan to generate isoeffect plots. Single agent and combination in vivo studies were also performed using MGI 114 against rhabdomyosarcoma and neuroblastoma xenograft models. RESULTS: After a 1-hour exposure to MGI 114, the mean IC50 (+/-standard error of mean) for medulloblastoma, neuroblastoma, Ewing sarcoma/primitive neuroectodermal tumor, and rhabdomyosarcoma cell lines were 1.58+/-0.51, 1.60+/-0.82, 1.18+/-0.08, and 3.99+/-1.69 microg/mL, respectively. When tumor cells were exposed concurrently to MGI 114 and topotecan, evidence of synergy was observed in 10 of 12 (83%) cell lines. Single agent and combination in vivo studies with MGI 114 showed that this agent had substantial, and at times curative, antitumor activity against rhabdomyosarcoma and neuroblastoma xenograft tumors. CONCLUSIONS: These data suggest that MGI 114 has significant efficacy as a single agent in preclinical studies against pediatric tumors. In addition, based on previous reports and the results presented here, combining MGI 114 with topotecan appears to be an attractive approach to the treatment of pediatric malignancies. After completion of the pediatric phase I studies of MGI 114, consideration should be given to phase II single agent and phase I combination studies with a topoisomerase I inhibitor such as topotecan or irinotecan.

Animals↗