A phase I clinical trial of spicamycin derivative KRN5500 (NSC 650426) using a phase I accelerated titration "2B" design

Investigational New Drugs

Volumn 21, Issue 1, 2003, Pages 63-74

  Gadgeel, S M ^a   Boinpally, R R ^a   Heilbrun, L K ^a   Wozniak, A ^a   Jain, V ^a   Redman, B ^b   Zalupski, M ^b   Wiegand, R ^a   Parchment, R ^a   LoRusso, P M ^a,c  

^a WAYNE STATE UNIVERSITY   (United States)

^b UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

^c HARPER UNIVERSITY HOSPITAL   (United States)

Author keywords

Clearance; Half life; Hepatotoxicity; MTD; Pharmacokinetics; Phase I clinical trial; Toxicity

Indexed keywords

6 [4 DEOXY 4 (2,4 TETRADECADIENOYLGLYCYLAMINO) GLYCERO BETA MANNOHEPTOPYRANOSYLAMINO] 9H PURINE; ALKALINE PHOSPHATASE; MITOMYCIN C; NITROSOUREA; NSC 650426; SPICAMYCIN;

ADULT; AGED; ALKALINE PHOSPHATASE BLOOD LEVEL; ALOPECIA; ANEMIA; ANOREXIA; ARTICLE; BLOOD TOXICITY; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CANCER; COMPARTMENT MODEL; CORRELATION ANALYSIS; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ERUPTION; DRUG INFUSION; DRUG TOLERABILITY; FATIGUE; FEMALE; FEVER; GASTROINTESTINAL TOXICITY; HUMAN; KIDNEY CANCER; KIDNEY FUNCTION; LIVER TOXICITY; LUNG CANCER; MALE; MELANOMA; NAUSEA; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SOLID TUMOR; SURVIVAL TIME; THROMBOCYTOPENIA; TITRIMETRY;

ADULT; AGED; ANTINEOPLASTIC AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; PURINE NUCLEOSIDES; TIME FACTORS; TREATMENT OUTCOME;

EID: 12444281852     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1022972427532     Document Type: Article

References (20)

1. Hayakawa Y, Nakagawa M, Kawai H, Tanabe K, Nakayama H, Shimazu A, Seto H, Otake N: Studies on the differentiation inducers of myeloid leukemic cells. III. Spicamycin, a new inducer of differentiation of HL-60 human promyelocytic leukemia cells. J Antibiot (Tokyo) 36(7): 934-937, 1983
2. Kawasaki K, Murakami T, Ita M, Sasaki K, Furukawa S: KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells. Cytometry 39(3): 211-216, 2000
3. Kamishohara M, Kawai H, Sakai T, Uchida T, Tsuruo T, Otake N: Inhibitory effect of a spicamycin derivative, KRN5500, on the growth of hepatic metastasis of human colon cancer-producing tissue polypeptide antigen. Cancer Chemother Pharmacol 38(6): 495-498, 1996
4. Kamishohara M, Kawai H, Odagawa A, Isoe T, Mochizuki J, Uchida T, Hayakawa Y, Seto H, Tsuruo T, Otake N: Structure-antitumor activity relationship of semi-synthetic spicamycin analogues. J Antibiot (Tokyo) 46(9): 1439-1446, 1993
5. Kamishohara M, Kawai H, Odagawa A, Isoe T, Mochizuki J, Uchida T, Hayakawa Y, Seto H, Tsuruo T, Otake N: Antitumor activity of SPM VIII, a derivative of the nucleoside antibiotic spicamycin, against human tumor xenografts. J Antibiot (Tokyo), 47(11): 1305-1311, 1994
6. Lee YS, Nishio K, Ogasawara H, Funayama Y, Ohira T, Saijo N: In vitro cytotoxicity of a novel antitumor antibiotic, spicamycin derivative, in human lung cancer cell lines. Cancer Res 55(5): 1075-1079, 1995
7. Stine KC, Warren BA, Saylors RL, Becton DL: KRN5500 induces apoptosis (PCD) of myeloid leukemia cell lines and patient blasts. Leuk Res 24(9): 741-749, 2000
8. Zhang WJ, Ohnishi K, Yoshida H, Pan L, Maksumova L, Muratkhodjaev F, Luo JM, Shigeno K, Fujisawa S, Naito K, Nakamura S, Shinjo K, Takeshita A, Ohno R: Spicamycin and KRN5500 induce apoptosis in myeloid and lymphoid cell lines with down-regulation of bcl-2 expression and modulation of promyelocytic leukemia protein. Jpn J Cancer Res 91(6): 604-611, 2000
9. Burger AM, Kaur G, Hollingshead M, Fischer RT, Nagashima K, Malspeis L, Duncan KL, Sausville EA: Antiproliferative activity in vitro and in vivo of the spicamycin analogue KRN5500 with altered glycoprotein expression in vitro. Clin Cancer Res 3(3): 455-463, 1997
10. Kamishohara M, Kawai H, Sakai T, Isoe T, Hasegawa K, Mochizuki J, Uchida T, Kataoka S, Yamaki H, Tsuruo T: Antitumor activity of a spicamycin derivative, KRN5500, and its active metabolite in tumor cells. Oncol Res 6(8): 383-390, 1994
11. Kawai H: Protein synthesis inhibitor - antitumor activity and mode of action of KRN5500. Gan To Kagaku Ryoho 24(11): 1571-1577, 1997
12. Simon R, Freidlin B, Rubinstein L, Arbuck SG, Collins J, Christian MC: Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89(15): 1138-1147, 1997
13. Hollander M, Wolfe DA: Nonparametric Statistical Methods. John Wiley and Sons Inc., New York, NY, 1973
14. Mehta C and Patel N: StatXact 5 Statistical Software for Exact Nonparametric Inference. Cytel Corp., Cambridge, MA, 2001
15. Yoshioka E, Morino M, Tanaka H, Shinkai H: Manual and automatic extraction and high-performance liquid chromatographic determination of a spicamycin derivative, KRN5500, in rat plasma. J Chromatogr B Biomed Sci Appl 691(2): 371-375, 1997
16. Levi F, Giacchetti S, Zidani R, Brezault-Bonnet C, Tigaud JM, Goldwasser F, Misset JL: Chronotherapy of colorectal cancer metastases. Hepatogastroenterology 48(38): 320-322, 2001
17. Matsumura Y, Yokoyama M, Kataoka K, Okano T, Sakurai Y, Kawaguchi T, Kakizoe T: Reduction of the side effects of an antitumor agent, KRN5500, by incorporation of the drug into polymeric micelles. Jpn J Cancer Res 90(1): 122-128, 1999
18. Misset JL, Levi F: Chronotherapy with 5-fluorouracil and other drugs in gastrointestinal malignancies. Chronotherapy Group of the European Organization for Research and Treatment of Cancer. Semin Oncol 27(5 Suppl 10): 78-82, 2000
19. Levi F: Therapeutic implications of circadian rhythms in cancer patients. Novartis Found Symp 227: 119-136; discussion 136-142, 2000
20. Takama H, Tanaka H, Sudo T, Tamura T, Tanigawara Y: Population pharmacokinetic modeling and model validation of a spicamycin derivative, KRN5500, in phase I study. Cancer Chemother Pharmacol 47(5): 404-410, 2001