A phase I trial of fixed dose rate gemcitabine plus capecitabine in metastatic cancer patients

被引:9
作者
Santini, D. [1 ]
Virzi, V. [1 ]
Vincenzi, B. [1 ]
Rocci, L. [1 ]
Leoni, V. [1 ]
Tonini, G. [1 ]
机构
[1] Univ Campus BioMed Rome, I-00155 Rome, Italy
关键词
capecitabine; fixed dose rate; gemcitabine; phase I study;
D O I
10.1093/annonc/mdl440
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Capecitabine and gemcitabine given as fixed dose rate (FDR) has not been demonstrated to be well tolerated in phase I previous studies. The goals of this phase I study were to determine the maximum-tolerated dose of this combination and to describe the dose-limiting toxic effects (DLT) and the safety profile of this way of administration. Patients and methods: Patients with advanced solid tumors were eligible for this study. Capecitabine was administered orally at a dose of 650 mg/m(2) bis in die (b.i.d.) for 14 consecutive days. Gemcitabine was administered at FDR of 10 mg/m(2) per min in escalating durations of infusion on days 1 and 8. The cycles were repeated every 21 days. Results: All 20 patients enrolled into the study were assessable for toxicity. Only one out of the first six patients treated at FDR gemcitabine dose of 800 mg/m(2) met protocol-specified DLT criteria (grade 4 neutropenia lasting >= 7 days) during the first two cycles. At these doses the majority of cycles of therapy were, however, delivered without dose reduction or delay. Another similar episode of DLT was observed at the same dose step among the following eight included patients. The dose of FDR gemcitabine 800 mg/m(2) in 80 min on days 1 and 8 plus capecitabine 650 mg/m(2) b.i.d., for 14 consecutive days followed by 1 week of rest is recommended for further study. Conclusion: The combination of FDR gemcitabine plus capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies.
引用
收藏
页码:576 / 580
页数:5
相关论文
共 15 条
  • [1] A PHASE-I CLINICAL, PLASMA, AND CELLULAR PHARMACOLOGY STUDY OF GEMCITABINE
    ABBRUZZESE, JL
    GRUNEWALD, R
    WEEKS, EA
    GRAVEL, D
    ADAMS, T
    NOWAK, B
    MINEISHI, S
    TARASSOFF, P
    SATTERLEE, W
    RABER, MN
    PLUNKETT, W
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (03) : 491 - 498
  • [2] Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial
    Burris, HA
    Moore, MJ
    Andersen, J
    Green, MR
    Rothenberg, ML
    Madiano, MR
    Cripps, MC
    Portenoy, RK
    Storniolo, AM
    Tarassoff, P
    Nelson, R
    Dorr, FA
    Stephens, CD
    VanHoff, DD
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (06) : 2403 - 2413
  • [3] CUNNINGHAM D, 2005, EUR J CANC S, V3
  • [4] GRUNEWALD R, 1990, CANCER RES, V50, P6823
  • [5] HEINEMANN V, 1990, MOL PHARMACOL, V38, P567
  • [6] Front-line therapy of advanced pancreatic cancer
    Kindler, HL
    [J]. SEMINARS IN ONCOLOGY, 2005, 32 (06) : S33 - S36
  • [7] POPLIN E, 2006, ASCO ANN M P 1 S, V24
  • [8] Clinical pharmacokinetics of capecitabine
    Reigner, B
    Blesch, K
    Weidekamm, E
    [J]. CLINICAL PHARMACOKINETICS, 2001, 40 (02) : 85 - 104
  • [9] Ren QF, 1998, CLIN CANCER RES, V4, P2811
  • [10] Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer
    Rini, BI
    Vogelzang, NJ
    Dumas, MC
    Wade, JL
    Taber, DA
    Stadler, WM
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (12) : 2419 - 2426