Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients

Clinical Cancer Research

Volumn 10, Issue 10, 2004, Pages 3377-3385

  Alexandre, Jérôme ^a   Raymond, Eric ^b   Kaci, Mahmoud Ould ^c   Brain, Etienne C ^d   Lokiec, François ^d   Kahatt, Carmen ^c   Faivre, Sandrine ^b   Yovine, Alejandro ^c   Goldwasser, François ^a   Smith, Sheri L ^e   MacDonald, John R ^e   Misset, Jean Louis ^f   Cvitkovic, Esteban ^c,f  

^a Hôpital Cochin ^*  (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c Cvitkovic et Associes Consultants   (France)

^d CENTRE RENÉ HUGUENIN   (France)

^e GUILFORD PHARMACEUTICALS INC   (United States)

^f SAINT LOUIS HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

6 HYDROXYMETHYLACYLFULVENE; IROFULVEN;

ADULT; AGED; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; CHEMOTHERAPY INDUCED EMESIS; CLINICAL TRIAL; CONSTIPATION; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; GASTROINTESTINAL SYMPTOM; HEADACHE; HEMATOLOGIC DISEASE; HUMAN; INFECTION; KIDNEY DISEASE; KIDNEY FUNCTION TEST; LEUKOPENIA; LIVER DISEASE; LIVER FUNCTION TEST; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; NAUSEA; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PHOTOPHOBIA; PRIORITY JOURNAL; RETINA CONE; SIDE EFFECT; SOLID TUMOR; STOMATITIS; THROMBOCYTOPENIA; TREATMENT OUTCOME; VISUAL DISORDER; VISUAL IMPAIRMENT;

ADULT; AGED; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, ALKYLATING; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; SESQUITERPENES; TIME FACTORS;

EID: 2542484489     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-03-0349     Document Type: Article

References (31)

1. McMorris TC, Kelner MJ, Wang W, Yu J, Estes L, Taetle R. (Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor properties. J Nat Prod 1996;59:896-9.
2. Kelner MJ, McMorris TC, Beck WT, Zamora JM, Taetle R. Preclinical evaluation of illudins as anticancer agents. Cancer Res 1987;47:3186-9.
3. MacDonald J, Dexter DL, Mangold G, et al. Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res 1997;57:279-83.
4. Marty J, MacDonald J, von Hoff DD, Weitman S. Antitumor activity of MGI 114 against human ovarian and pancreatic tumor xenograft models. Proc Am Assoc Cancer Res 1999;40:123.
5. Friedman H, Keir S, Houghton P, Lawless AA, Bigner DD, Waters S. Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice. Proc Am Assoc Cancer Res 2001;42:325.
6. Kelner MJ, McMorris TC, Estes L, Samson K, Bagnell CR, Taetle R. Efficacy of MGI 114 (6-hydroxymethylacylfulvene, HMAF) against the mdrl/gp170 metastatic MV522 lung carcinoma xenograft. Eur J Cancer 1998;34:908-13.
7. Kelner MJ, McMorris TC, Estes L, Oval M, Rojas R, Samson K. Efficacy of MGI 114 against the MRP-positive MV522 lung carcinoma xenograft. Proc Am Assoc Cancer Res 1999;40:300.
8. Woynarowski J, Napier C, Koester S, et al. Effects on DNA integrity and apoptosis induction by a novel antitumor sesquiterpene drug, 6-hydroxymethylacylfulvene (HMAF). Biochem Pharmacol 1997;54:1181-93.
9. Herzig M, Arnett B, MacDonald J, Woynarowski J. Drug uptake and cellular targets of hydroxymethylacylfulvene (HMAF). Biochem Pharmacol 1999;58:217-25.
10. Poindessous V, Koeppel F, Raymond E, Comisso M, Waters JS, Larsen A. Marked activity of irofulven toward human carcinoma cells: Comparison with cisplatin and ecteinascidin. Clin Cancer Res 2003;9:2817-25.
11. Poindessous V, Koeppel F, Hubert C, Comisso M, Raymond E, Larsen A. Concentration and time-dependent cytotoxic effects of irofulven (MGI-114) in a panel of 28 human cancer cell lines (comparison with cisplatin and ecteinascidin 743). Clin Cancer Res 2001;7:3695S.
12. Koeppel F, Poindessous V, Lemke K, Skladanwski A, Raymond E, Larsen A. Irofulven-resistant colon carcinoma cells show little or no cross-resistance with several anticancer drug types. Clin Cancer Res 2001;7:3696s.
13. Izbicka E, Davidson K, Lawrence R, Cote R, MacDonald J, von Hoff DD. Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression. Anticancer Res 1999;19:1299-307.
14. Liang H, Herzig M, Salinas R, et al. Pro-oxidative distortion of the cellular redox-homeostasis in irofulven-induced apoptosis. Clin Cancer Res 2001;7:3723s.
15. Sato Y, Kashimoto S, MacDonald JR. In vivo antitumour efficacy of MGI-114 (6-hydroxymethylacylfulvene, HMAF) in various human tumour xenograft models including several lung and gastric tumours. Eur J Cancer 2001;37:1419-28.
16. Eckhardt S, Baker SD, Britten C, et al. Phase I and pharmacokinetic study of irofulven, a novel mushroom-derived cytotoxin, administered for five consecutive days every four weeks in patients with advanced solid malignancies. J Clin Oncol 2000;18:4086-97.
17. Reed E, Sarosy G, Gordon A, Weems G, Herdrich L. Clinical activity of irofulven in pretreated advanced ovarian cancer (AOC) patients. Clin Cancer Res 2001;7:3697s.
18. von Hoff DD, Cox JV, Eder J, et al. Activity of irofulven (MGI 114) in patients with advanced pancreatic cancer refractory to gemcitabine. Clin Cancer Res 2000;6:4539s.
19. Senzer N, Rakvica R, Chao H, Smith S. A Phase II Trial of MGI 114 in patients with hormone-refractory prostate cancer. Proc Am Soc Clin Oncol 1999;18:321a.
20. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer (Phila) 1981;47:207-14.
21. Urien S, Alexandre J, Raymond E, et al. Phase I population pharmacokinetics of irofulven. Anticancer Drugs 2003;14:353-8.
22. Dowell JE, Johnson D, Rogers JS, et al. A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy. Investig New Drugs 2001;19:85-8.
23. Witta S, Eckhardt G, Rothenberg M, et al. A phase I combination trial of irofulven and gemcitabine in patients with advanced solid malignancies. Proc Am Soc Clin Oncol 2003;22:138.
24. McCreery H, Rowinsky E, Tolcher AW, et al. Phase I trial of irofulven and CPT-11 in patients with advanced cancers. Proc Am Soc Clin Oncol 2002;21:82b.
25. Hilgers W, Alexandre J, Goldwasser F, et al. Phase I and pharmacokinetic study of irofulven (IROF) in combination with cisplatin (CDDP), given every 2 weeks, in patients (pts) with advanced solid tumors. Proc Am Soc Clin Oncol 2003;22:152.
26. Alexandre J, Bertheault-Cvitkovic F, Hilgers W, Yovine A, Weems G, Herait P. Phase I and pharmacokinetic (PK) study of irofulven (IROF) and capecitabine (CAP) in combination using an intermittent schedule in advanced solid tumors. Proc Am Soc Clin Oncol 2003;22:154.
27. Van Laar E, Rothe M, Quada J, Weitman S, MacDonald J, Waters JS. Antitumor activity of Irofulven against the MiaPaCa pancreatic tumor xenograft model: Evaluation of daily and intermittent dose schedules. Clin Cancer Res 2001;7:3730s-1s.
28. Britten C, Hilsenbeck S, Eckhardt S, et al. Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. Cancer Res 1999;59:1049-53.
29. Weitman S, Stinger S, Waters S, MacDonald J. Antitumor activity of irofulven (MGI114) in combination with taxoterre against DU145 human prostate tumor xenograft model. Proc Am Assoc Cancer Res 2001;42:88.
30. Hammond L, Hilsenbeck S, Eckhardt S, et al. Enhanced antitumour activity of 6-hydroxymethylacylfulvene in combination with topotecan or paclitaxel in the MV522 lung carcinoma xenograft model. Eur J Cancer 2000;36:2430-6.
31. Debono J, Rowinsky E, Hidalgo M, et al. Irofulven in combination with irinotecan: A Phase I study examining 3 schedules in patients with advanced cancers. Clin Cancer Res 2001;7:3796s.