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Titolo:
Phase II study of 4-ipomeanol, a naturally occurring alkylating furan, in patients with advanced hepatocellular carcinoma
Autore:
Lakhanpal, S; Donehower, RC; Rowinsky, EK;
Indirizzi:
Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA Canc Therapy & Res Ctr San Antonio TX USA 78229 San Antonio, TX 78229 USA Univ Texas, Hlth Sci Ctr, San Antonio, TX USA Univ Texas San Antonio TX USA v Texas, Hlth Sci Ctr, San Antonio, TX USA
Titolo Testata:
INVESTIGATIONAL NEW DRUGS
fascicolo: 1, volume: 19, anno: 2001,
pagine: 69 - 76
SICI:
0167-6997(200102)19:1<69:PISO4A>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
POTATOES IPOMOEA-BATATAS; METABOLIC-ACTIVATION; COVALENT BINDING; LUNG-CANCER; REACTIVE METABOLITES; RABBIT PULMONARY; DOSE SCHEDULE; CELL-LINES; TOXICITY; GLUTATHIONE;
Keywords:
4-Ipomeanol; hepatocellular carcinoma; liver cancer; hepatoma; alkylating agent; phase II;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Rowinsky, EK Canc Therapy & Res Ctr, Inst Drug Dev, 8122 Datapoint Dr,Suite 700, San Antonio, TX 78229 USA Canc Therapy & Res Ctr 8122 Datapoint Dr,Suite 700 San Antonio TX USA 78229
Citazione:
S. Lakhanpal et al., "Phase II study of 4-ipomeanol, a naturally occurring alkylating furan, in patients with advanced hepatocellular carcinoma", INV NEW DR, 19(1), 2001, pp. 69-76

Abstract

Background/purpose: 4-Ipomeanol (IPO; NSC 394438), a naturally occurring furan isolated from common sweet potatoes (Ipomoea batatas) infected with the fungus Fusarium solani was the first agent to be developed by the National Cancer Institute based on a biochemical-biological rationale as an anticancer agent targeted specifically against lung cancer. Prior to clinical development, IPO was shown to induce pulmonary toxicity in the lungs of several mammalian species because the agent is metabolized to a highly reactive furan epoxide by specific cytochrome P450 monooxygenases found in pulmonary Clara cells and type II pneumocytes, which share biochemical features with bronchogenic carcinoma. However, instead of inducing the anticipated lung toxicity in patients with lung cancer in disease-directed phase I studies, hepatotoxicity was the principal toxic effect of IPO in humans. Based on thepresumption that IPO may be preferentially activated by cytochrome P450 monooxygenases in liver cells and biochemically-related hepatic malignancies,a phase II study was conducted to determine the activity and evaluate the toxicity of IPO in patients with advanced hepatocellular carcinoma. Patients and methods: Nineteen patients with advanced measurable hepatocellular carcinoma were enrolled on the phase II trial. All patients had an Eastern Cooperative Oncology Group performance status of at least two, no evidence ofpulmonary dysfunction, and had either no prior treatment or minimal prior therapy. Patients were treated with IPO at a dose of either 1032 mg/m(2), which was the maximum tolerated and recommended phase II dose previously derived for patients with normal hepatic function (15 patients) or 826 mg/m(2)if they had serum bilirubin concentrations in the range of 2.0 to 3.0 mg/dL (four patients). Treatment was repeated every three weeks. Objective tumor response, the primary endpoint of the study, was assessed after every twocourses of treatment, and both pulmonary function and lung density were rigorously monitored using successive pulmonary function testing and computerized tomography. Results: All nineteen patients were evaluable for both response and toxicity. No major objective responses were observed. One patienthad a minor, brief reduction in lung metastases. Although marker lesions and overall disease remained stable for at least 12 and 24 months in three and two patients, respectively, the median time to progression was three months and the median survival was five months for all patients. The principaltoxicity was reversible elevations in hepatic transaminases, which occasionally resulted in dose reduction. No clinically-significant pulmonary toxicity was noted. Conclusion: IPO at a dose of either 826 or 1032 mg/m(2) administered every three weeks did not demonstrate a relevant degree of clinical activity against advanced hepatocellular carcinoma. Further evaluations of TO is not recommended for this disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 10:12:23