First-time-in-man and pharmacokinetic study of weekly oral perifosine in patients with solid tumours

European Journal of Cancer

Volumn 46, Issue 5, 2010, Pages 920-925

  Unger, Clemens ^a   Berdel, Wolfgang ^b   Hanauske, Axel R ^c   Sindermann, Herbert ^d   Engel, Jürgen ^d   Mross, Klaus ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c DEPARTMENT OF CARDIOLOGY   (Germany)

^d Aeterna Zentaris GmbH   (Germany)

Author keywords

AEZS 104; Akt inhibition; D 21266; Oral medication; Perifosine; Phase I

Indexed keywords

ALIZAPRIDE; ANTIDIARRHEAL AGENT; DEXAMETHASONE; PERIFOSINE; SEROTONIN 3 ANTAGONIST; TROPISETRON;

ABDOMINAL PAIN; ADULT; AGED; ARTHRALGIA; ARTICLE; BRADYCARDIA; CLINICAL ARTICLE; DIARRHEA; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG URINE LEVEL; DRUG WITHDRAWAL; DYSPHONIA; DYSPNEA; ERYTHEMA; FATIGUE; FEMALE; GASTRITIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYPOTENSION; KIDNEY FUNCTION; LIFE EXPECTANCY; LIVER FUNCTION; MALE; MAXIMUM TOLERATED DOSE; MYALGIA; NAUSEA; PERIPHERAL EDEMA; PRIORITY JOURNAL; SIDE EFFECT; SOLID TUMOR; SPUTUM; SWEATING; TANDEM MASS SPECTROMETRY; TASTE; TIME TO MAXIMUM PLASMA CONCENTRATION; TONGUE; URINARY EXCRETION; VOMITING; WORLD HEALTH ORGANIZATION;

ABDOMINAL PAIN; ADMINISTRATION, ORAL; ANTIEMETICS; ANTINEOPLASTIC AGENTS; DIARRHEA; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NAUSEA; NEOPLASMS; PHOSPHORYLCHOLINE; TREATMENT OUTCOME; VOMITING;

EID: 77649144161     PISSN: 09598049     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejca.2009.12.028     Document Type: Article

References (18)

1. Unger C., Sindermann H., Peukert M., et al. Hexadecylphosphocholine in the topical treatment of skin metastases in breast cancer patients. Prog Exp Tumor Res 34 (1992) 153-159
2. Sundar S., Jha T.K., Thakur C.P., et al. Oral miltefosine for Indian visceral leishmaniasis. New Engl J Med 347 (2002) 1739-1746
3. Danhauser-Riedl S., Drozd A., Zafferani M., et al. Phase I study with weekly oral miltefosine (hexadecyl-phosphocholine) in cancer patients. Onkologie 14 (1991) 392-400
4. Verweij J., Planting A., van der Burg M., and Stoter G. A dose-finding study of miltefosine (hexadecylphosphocholine) in patients with metastatic solid tumours. J Cancer Res Clin Oncol 118 (1992) 606-608
5. Hilgard P., Klenner T., Stekar J., Nössner G., Kutscher B., and Engel J. D-21266, a new heterocyclic alkylphospholipid with antitumor activity. Eur J Cancer 33 (1997) 442-446
6. Vink S.R., Lagerwerf S., Mesman E., et al. Radiosensitization of squamous cell carcinoma by the alkylphospolipid perifosine in cell culture and xenografts. Clin Cancer Res 12 (2006) 1612-1622
7. Ruiter G.A., Zerp S.F., Bartelink H., van Blitterswijk W.J., and Verheij M. Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway. Anticancer Drugs 14 (2003) 167-173
8. Ruiter G.A., Zerp S.F., Bartelink H., van Blitterswijk W.J., and Verheij M. Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer Res 59 (1999) 2457-2463
9. Ruiter G.A., Verheij M., Zerp S.F., Moolenaar W.H., and Van Blitterswijk W.J. Submicromolar doses of alkyl-lysophospholipids induce rapid internalization, but not activation, of epidermal growth factor receptor and concomitant MAPK/ERK activation in A431 cells. Int J Cancer 102 (2002) 343-350
10. Kondapaka SB, Singh SS, Dasmahapatra GP, Sausville EA, Roy KK. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol Cancer Ther 2003;11:1093-1103.
11. Hideshima T., Catley L., Raje N., et al. Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells. Brit J Haematol 138 (2007) 783-791
12. Knebel N.G., Grieb S., Winkler M., et al. Quantification of perifosine, an alkylphosphocholine anti-tumour agent, in plasma by pneumatically assisted electrospray tandem mass spectrometry coupled with high-performance liquid chromatography. J Chromatogr B: Biomed Sci Appl 721 (1999) 257-269
13. Crul M., Rosing H., de Klerk G.J., et al. Phase I and pharmacological study daily oral administration of perifosine (D-21266) in patients with advanced solid tumours. Eur J Cancer 38 (2002) 1615-1621
14. Van Ummersen L., Binger K., Volkmann J., et al. A phase I trial of perifosine (NSC 639966) on a loading dose/maintenance dose schedule in patients with advanced cancer. Clin Cancer Res 10 (2004) 7450-7456
15. Pronk L.C., Planting A.S.Th., van Oosterom A., et al. Increases in leucocyte and platelet counts induced by the alkyl phospholipid hexadecylphosphocholine. Eur J Cancer 30A (1994) 1019-1022
16. Vink S., Schellens J.H.M., Beijnen J.H., et al. Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumors. Radiother Oncol 80 (2006) 207-213
17. Bailey H.H., Mahoney M.R., Ettinger D.S., et al. Phase II study of oral perifosine in patients with advanced soft tissue sarcoma. Cancer 107 (2006) 2462-2467
18. Ghobrial IM, Leleu X, Rubin N, et al. Phase II trial of the novel oral Akt inhibitor perifosine in relapsed and/or refractory Waldenstrom macroglobulinemia (WM). ASCO Meeting Abstracts (J Clin Oncol) 2008;26:8546.