Combined phase I/II study of imexon (AOP99.0001) for treatment of relapsed or refractory multiple myeloma

Anti-Cancer Drugs

Volumn 21, Issue 7, 2010, Pages 708-715

  Moehler, Thomas M ^a   Feneberg, Reinhard ^a   Ho, Anthony Dick ^a   Golenkov, Anatoly K ^d   Ludwig, Heinz ^e   Kropff, Martin ^b   Khuageva, Nuriet K ^d   Hajda, Jacek ^a   Von Broen, Ingo ^c   Goldschmidt, Hartmut ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c Wilex Biotechnology GmbH   (Germany)

^d SP Botkin Moscow City Clinical Hospital   (Russian Federation)

^e UNIVERSITY OF VIENNA   (Austria)

Author keywords

imexon; myeloma; phase I clinical study

Indexed keywords

AOP 99 0001; AOP 99 0002; BETA 2 MICROGLOBULIN; BORTEZOMIB; CREATININE; CYCLOPHOSPHAMIDE; DRUG METABOLITE; HEMOGLOBIN; IMEXON; MELPHALAN; PREDNISONE; THALIDOMIDE; UNCLASSIFIED DRUG; VINCRISTINE;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ADULT; AGED; ANEMIA; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BACKACHE; BLEEDING; BONE NECROSIS; BONE PAIN; BRONCHITIS; CARDIOMYOPATHY; CATHETER INFECTION; CHRONIC PANCREATITIS; CLINICAL ARTICLE; CLINICAL TRIAL; CONSTIPATION; COUGHING; CREATININE BLOOD LEVEL; DIARRHEA; DISEASE DURATION; DIZZINESS; DOSE RESPONSE; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; EPIGASTRIC DISCOMFORT; EPISTAXIS; FATIGUE; FEMALE; FEVER; FLUSHING; HEADACHE; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART FAILURE; HEMOGLOBIN BLOOD LEVEL; HERPES SIMPLEX; HUMAN; HYPERTENSION; INSOMNIA; LACTATE DEHYDROGENASE BLOOD LEVEL; LEUKOPENIA; LIMB PAIN; MAJOR DEPRESSION; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MORTALITY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; OLIGURIA; OPEN STUDY; PARESTHESIA; PERIODONTITIS; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHLEBITIS; PNEUMONIA; POLLAKISURIA; POLYNEUROPATHY; PRIORITY JOURNAL; PROTEINURIA; RECOMMENDED DRUG DOSE; RESTLESSNESS; RHINITIS; RHINOPHARYNGITIS; SEPSIS; SEPTICEMIA; SHOULDER PAIN; SIDE EFFECT; SOMNOLENCE; STOMATITIS; STRESS; SUPRAVENTRICULAR TACHYCARDIA; TACHYCARDIA; THORAX PAIN; THROMBOCYTOPENIA; THROMBOPHLEBITIS; TREATMENT DURATION; TREMOR; TRIACYLGLYCEROL BLOOD LEVEL; UREA BLOOD LEVEL; URINARY EXCRETION; URINARY TRACT INFECTION; VOMITING;

ADULT; AGED; ANTINEOPLASTIC AGENTS; APOPTOSIS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEXANONES; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MULTIPLE MYELOMA; OXIDATIVE STRESS; RECURRENCE; TREATMENT OUTCOME;

EID: 77954658758     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/CAD.0b013e32833b975b     Document Type: Article

References (16)

1. Kastritis E, Zervas K, Symeonidis A, Terpos E, Delimbassi S, Anagnostopoulos N, et al. Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia 2009; 23:1152-1157.
2. Moehler TM, Neben K, Benner A, Egerer G, Krasniqi F, Ho AD, et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001; 98:3846-3848.
3. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111:2516-2520.
4. Bicker UF. BM 06.002: A new immunostimulating compound. In: Chirigos MA, editor. Immune modulation and control of neoplasia by adjuvant therapy. New York: Raven Press; 1978. pp. 389-401.
5. Sagaster P, Kokoschka EM, Kokron O, Micksche M. Antitumor activity of imexon. J Natl Cancer Inst 1995; 87:935-936.
6. Salmon SE, Hersh EM. Sensitivity of multiple myeloma to imexon in the human tumor cloning assay. J Natl Cancer Inst 1994; 86:228-230.
7. Dvorakova K, Waltmire CN, Payne CM, Tome ME, Briehl MM, Dorr RT. Induction of mitochondrial changes in myeloma cells by imexon. Blood 2001; 97:3544-3551.
8. Evens AM, Prachand S, Shi B, Paniaqua M, Gordon LI, Gartenhaus RB. Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent. Clin Cancer Res 2004; 10:1481-1491.
9. Samulitis BK, Landowski TH, Dorr RT. Inhibition of protein synthesis by imexon reduces HIF-1alpha expression in normoxic and hypoxic pancreatic cancer cells. Invest New Drugs 2009; 27:89-98.
10. Engel RH, Evens AM. Oxidative stress and apoptosis: a new treatment paradigm in cancer. Front BioSci 2006; 11:300-312.
11. Micksche M, Kokoschka EM, Sagaster P, Bicker UF. Phase I study of immunotherapy with Imexon. In: Chirigos MA, editor. Immune modulation and control of neoplasia by adjuvant therapy. New York: Raven Press; 1978. pp. 403-413.
12. Dragovich T, Gordon M, Mendelson D,Wong L, Modiano M, Chow HH, et al. Phase I trial of imexon in patients with advanced malignancy. J Clin Oncol 2007; 25:1779-1784.
13. Moulder S, Dhillon N, Ng C, Hong D,Wheler J, Naing A, et al. A phase I trial of imexon, a pro-oxidant, in combination with docetaxel for the treatment of patients with advanced breast, non-small cell lung and prostate cancer. Invest New Drugs 2009 [E-pub ahead of print].
14. Scott J, Dorr RT, Samulitis B, Landowski TH. Imexon-based combination chemotherapy in A375 human melanoma and RPMI 8226 human myeloma cell lines. Cancer Chemother Pharmacol 2007; 59:749-757.
15. Nair B, Shaughnessy JD Jr, Zhou Y, Astrid-Cartron M, Qu P, van Rhee F, et al. Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival. Blood 2009; 113:6572-6575.
16. Hose D, Reme T, Meissner T, Moreaux J, Seckinger A, Lewis J, et al. Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma. Blood 2009; 113:4331-4340.