Dose-finding phase I and pharmacokinetic study of capecitabine (Xeloda) in combination with epirubicin and cyclophosphamide (CEX) in patients with inoperable or metastatic breast cancer

Oncology

Volumn 72, Issue 5-6, 2008, Pages 330-337

  Saji, Shigehira ^a   Toi, Masakazu ^d   Morita, Satoshi ^d   Iwata, Hiroji ^e   Ito, Yoshinori ^b   Ohno, Shinji ^f   Kobayashi, Tadashi ^c   Hozumi, Yasuo ^g   Sakamoto, Junichi ^h  

^a TOKYO METROPOLITAN KOMAGOME HOSPITAL   (Japan)

^b CANCER INSTITUTE HOSPITAL   (Japan)

^c JIKEI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^d KYOTO UNIVERSITY   (Japan)

^e AICHI CANCER CENTER HOSPITAL   (Japan)

^f NATIONAL KYUSHU CANCER CENTER   (Japan)

^g JICHI MEDICAL UNIVERSITY   (Japan)

^h NAGOYA UNIVERSITY   (Japan)

Author keywords

Breast cancer; Capecitabine; Epirubicin; Pharmacokinetics; Phase I study

Indexed keywords

5' DEOXY 5 FLUOROCYTIDINE; CAPECITABINE; CYCLOPHOSPHAMIDE; DOXIFLURIDINE; EPIRUBICIN;

ADULT; AGED; ALOPECIA; ANEMIA; ANOREXIA; ARTICLE; BREAST CANCER; CLINICAL ARTICLE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONSTIPATION; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HAND FOOT SYNDROME; HUMAN; INFECTION; INOPERABLE CANCER; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAIL; NAUSEA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; TASTE; THROMBOCYTOPENIA; TREATMENT RESPONSE; VASCULITIS; VOMITING;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CYCLOPHOSPHAMIDE; DEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; EPIRUBICIN; FEMALE; FLUOROURACIL; HUMANS; MIDDLE AGED;

EID: 39049172914     PISSN: 00302414     EISSN: None     Source Type: Journal    
DOI: 10.1159/000113062     Document Type: Article

References (30)

1. Hortobagyi GN: Treatment of breast cancer. N Engl J Med 1998;339:974-984.
2. Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thurlimann B, Senn HJ: Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 2005;16:1569-1583.
3. Trent JC, Valero V, Booser DJ, Esparza-Guerra LT, Ibrahim N, Rahman Z, Vernillet L, Patel S, David CL, Murray JL, Cristofanilli M, Hortobagyi GN: A phase I study of docetaxel plus cyclophosphamide in solid tumors followed by a phase II study as first-line therapy in metastatic breast cancer. Clin Cancer Res 2003;9:2426-2434.
4. Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L: Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 2006;24:5381-5387.
5. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274-1281.
6. Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B: Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 2000;45:291-297.
7. Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H: Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 1998;4:1013-1019.
8. Endo M, Shinbori N, Fukase Y, Sawada N, Ishikawa T, Ishitsuka H, Tanaka Y: Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5′-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models. Int J Cancer 1999;83:127-134.
9. Toi M, Atiqur Rahman M, Bando H, Chow LW: Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment. Lancet Oncol 2005;6:158-166.
10. Blum JL, Jones SE, Buzdar AU, LoRusso PM, Kuter I, Vogel C, Osterwalder B, Burger HU, Brown CS, Griffin T: Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999;17:485-493.
11. Blum JL, Dieras V, Lo Russo PM, Horton J, Rutman O, Buzdar A, Osterwalder B: Multicenter, phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients. Cancer 2001;92:1759-1768.
12. O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R: Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002;20:2812-2823.
13. Blum JL, Dees EC, Chacko A, Doane L, Ethirajan S, Hopkins J, McMahon R, Merten S, Negron A, Neubauer M, Ilegbodu D, Boehm KA, Asmar L, O'Shaughnessy JA: Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 2006;24:4384-4390.
14. Gradishar WJ, Meza LA, Amin B, Samid D, Hill T, Chen YM, Lower EE, Marcom PK: Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study. J Clin Oncol 2004;22:2321-2327.
15. Xu L, Song S, Zhu J: A phase II trial of trastuzumab (H) + capecitabine (X) as first-line treatment in patients (pts) with HER2-positive metastatic breast cancer (MBC). Ann Oncol 2006;17(suppl 9):169P.
16. Wardley A, Anton-Torres A, Pivot X: Trastuzumab plus docetaxel with or without capecitabine in patients with HER2-positive advanced/metastatic breast cancer: primary efficacy results from a randomised phase II study (CHAT). Ann Oncol 2006;17(suppl 9):LBA6.
17. Lybaert W, Wildiers H, Neven P: Multicentre phase II study of capecitabine (X), docetaxel (T) ± trastuzumab (H) as neoadjuvant treatment for patients (pts) with locally advanced breast cancer (LABC): preliminary safety and efficacy results. Ann Oncol 2006;17(suppl 9):154P.
18. Venturini M, Durando A, Garrone O, Colozza MA, Contu A, Stevani I, Genta F, Bighin C, Lambiase A, Del Mastro L: Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated, advanced breast carcinoma. Cancer 2003;97:1174-1180.
19. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006;355:2733-2743.
20. Joensuu H, Hemminki A, Tanner M: Phase III, randomized study of docetaxel (T) + capecitabine (X) (TX) followed by cyclophosphamide (C) + epirubicin (E) + X (CEX) vs. T followed by C + E + fluorouracil (F) (CEF) as adjuvant treatment for patients (pts) with early breast cancer (BC): an interim safety analysis. Proc Am Soc Clin Oncol 2005;23(suppl):719.
21. Roché H, Deporte R, Berton-Rigaud D: Updated safety findings from a randomized phase II trial of capecitabine + epirubicin + cyclophosphamide (CEX) vs. 5-FU epirubicin + cyclophosphamide (FEC) as neoadjuvant therapy in patients (pts) with operable breast cancer (BC). Ann Oncol 2006;17(suppl 9):261P.
22. Bonnefoi H, Biganzoli L, Mauriac L, Cufer T, Schaefer P, Atalay G, Piccart M: An EORTC phase I study of capecitabine (Xeloda) in combination with fixed doses of cyclophosphamide and epirubicin (CEX) as primary treatment for large operable or locally advanced/ inflammatory breast cancer. Eur J Cancer 2003;39:1277-1283.
23. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs 2000;18:343-354.
24. O'Quigley J, Pepe M, Fisher L: Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics 1990;46:33-48.
25. Ishizuka N, Morita S: Practical implementation of the continual reassessment method; in Crowley J, Ankerst DP (eds): Handbook of Statistics in Clinical Oncology, ed 2. Boca Raton, CRC Press, 2005.
26. Morita S, Toi M, Kobayashi T, Ito Y, Hozumi Y, Ohno S, Iwata H, Sakamoto J: Application of a continual reassessment method to a phase I clinical trial of capecitabine in combination with cyclophosphamide and epirubicin (CEX) for inoperable or recurrent breast cancer. Jpn J Clin Oncol 2004;34:104-106.
27. Ebi H, Sigeoka Y, Saeki T, Kawada K, Igarashi T, Usubuchi N, Ueda R, Sasaki Y, Minami H: Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives, capecitabine and 5′-deoxy-5-fluorouridine (5′-DFUR). Cancer Chemother Pharmacol 2005;56:205-211.
28. Reigner B, Blesch K, Weidekamm E: Clinical pharmacokinetics of capecitabine. Clin Pharmacokinet 2001;40:85-104.
29. Villalona-Calero MA, Weiss GR, Burris HA, Kraynak M, Rodrigues G, Drengler RL, Eckhardt SG, Reigner B, Moczygemba J, Burger HU, Griffin T, Von Hoff DD, Rowinsky EK: Phase I and pharmacokinetic study of the oral fluoropyrimidine capecitabine in combination with paclitaxel in patients with advanced solid malignancies. J Clin Oncol 1999;17:1915-1925.
30. Pronk LC, Vasey P, Sparreboom A, Reigner B, Planting AS, Gordon RJ, Osterwalder B, Verweij J, Twelves C: A phase I and pharmacokinetic study of the combination of capecitabine and docetaxel in patients with advanced solid tumours. Br J Cancer 2000;83:22-29.