A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

British Journal of Cancer

Volumn 103, Issue 9, 2010, Pages 1362-1368

  Van Herpen, C M L ^a   Eskens, F A L M ^b   De Jonge, M ^b   Desar, I ^a   Hooftman, L ^c   Bone, E A ^c   Timmer Bonte, J N H ^a   Verweij, J ^b  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c Chroma Therapeutics Ltd   (United Kingdom)

Author keywords

aminopeptidase inhibitor; CHR 2797; paclitaxel; Phase I; tosedostat

Indexed keywords

ANTINEOPLASTIC AGENT; CHR 2797; PACLITAXEL; TOSEDOSTAT; UNCLASSIFIED DRUG;

ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BACKACHE; BILIRUBIN BLOOD LEVEL; BLADDER CANCER; BRONCHITIS; CANCER PAIN; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CANCER; CONSTIPATION; CONTROLLED STUDY; COUGHING; CYSTITIS; DEHYDRATION; DIABETES MELLITUS; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG ERUPTION; DRUG FEVER; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; DYSPNEA; EDEMA; ERYTHEMA; FATIGUE; FEMALE; FLUID INTAKE; HUMAN; HYPERCALCEMIA; HYPERGLYCEMIA; HYPERHIDROSIS; INFUSION REACTION; INJECTION SITE REACTION; KIDNEY FAILURE; LEUKOCYTE; LEUKOPENIA; LUNG EMBOLISM; LUNG NON SMALL CELL CANCER; LYMPHOCYTE; LYMPHOCYTE COUNT; MALAISE; MALE; MAXIMUM ALLOWABLE CONCENTRATION; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MYALGIA; MYOCARDITIS; NAUSEA; NEUTROPENIA; NEUTROPHIL; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL; POLLAKISURIA; PRIORITY JOURNAL; PRURITUS; RHINOPHARYNGITIS; SARCOMA; SENSORY NEUROPATHY; SIDE EFFECT; SOLID TUMOR; SPINAL CORD COMPRESSION; STOMACH CANCER; STOMACH DISTENSION; THROMBOCYTE; TREATMENT RESPONSE; URINARY TRACT INFECTION; VOMITING;

ADULT; AGED; AMINOPEPTIDASES; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DRUG ADMINISTRATION SCHEDULE; FATIGUE; FEMALE; GLYCINE; HUMANS; HYDROXAMIC ACIDS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; PACLITAXEL;

EID: 77958562812     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/sj.bjc.6605917     Document Type: Article

References (14)

1. Bristol Myers Squibb (SPC) (2005) Taxol Summary of Product Characteristics. Report. Bristol Myers Squibb: UK
2. Ginsberg F, Parrillo JE (2005) Eosinophilic myocarditis. Heart Fail Clin 1: 419-429
3. Gradishar WJ (2006) Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother 7(8): 1041-1053. Review.
4. Ichinose Y, Genka K, Koike T, Harubumi K, Watanabe Y, Mori T, Ilioka S, Sakuma A, Ohta M (2003) Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma. J Natl Cancer Inst 95(8): 605-610
5. Jenkins C, Mills K, Pepper C, Burnett A (2007) Cellular aminopeptidase inhibition as a target for the therapy of AML by the novel agent tosedostat. Blood 110(11): Abstract No. 1608
6. Krige D, Needham LA, Bawden LJ, Flores N, Farmer H, Miles LE, Stone E, Callaghan J, Chandler S, Clark VL, Kirwin-Jones P, Legris V, Owen J, Patel T, Wood S, Box G, Laber D, Odedra R, Wright A, Wood LM, Eccles SA, Bone EA, Ayscough A, Drummond AH (2008) CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res 68: 6669-6679
7. Markham M, Kennedy A, Webster K, Kulp B, Peterson G, Belinson J (2000) Paclitaxel associated hypersensitivity reactions: experience of the gynecological oncology program of the cleveland clinic cancer center. J Clin Oncol 18(1): 102-105
8. Moore HE, Davenport EL, Smith EM, Muralikrishnan S, Dunlop AS, Walker BA, Krige D, Drummond AH, Hooftman L, Morgan GJ, Davies FE (2009)Aminopeptidase inhibition as a targeted treatment strategy in myeloma. Mol Cancer Ther 8(4): 762-770
9. Ossenkoppele G, Hooftman W, Zweegman S, Davies F, Morgan G, Mueller-Tidow C, Krug U, Duhrsen U, Burnett A, Jenkins C, Zachee P, Dierickx D, Lowenberg P, Sonneveld P, Hooftman L, Richardson A (2009) A multicentre Phase I-II study of tosedostat in the treatment of patients with relapsed or refractory acute myeloid leukaemia. Haematologica 94(s2): Ref Type: Abstract 1065
10. Reid AH, Protheroe A, Attard G, Hayward N, Vidal L, Spicer J, Shaw HM, Bone EA, Carter J, Hooftman L, Harris A, De Bono JS (2009) A first-in-man phase i and pharmacokinetic study on CHR-2797 (Tosedostat), an inhibitor of M1 aminopeptidases, in patients with advanced solid tumors. Clin Cancer Res 15: 4978-4985
11. Saric T, Graef CI, Goldberg AL (2004) Pathway for degradation of peptides generated by proteasomes: a key role for thimet oligopeptidase and other metallopeptidases. J Biol Chem 279(45): 46723-46732
12. Talmadge JE, Lenz BF, Pennington R, Long C, Phillips H, Schneider M, Tribble H (1986) Immunomodulatory and therapeutic properties of bestatin in mice. Cancer Res 46: 4505
13. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, van GM, Van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92: 205-216
14. Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, Baker Jr JR (1990) Hypersensitivity reactions from taxol. J Clin Oncol 8: 1263-1268