PMID- 11800031
OWN - NLM
STAT- MEDLINE
DCOM- 20020130
LR  - 20190901
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 48
IP  - 6
DP  - 2001 Dec
TI  - Phase I trial of capecitabine in combination with interferon alpha in patients 
      with metastatic renal cancer: toxicity and pharmacokinetics.
PG  - 493-8
AB  - PURPOSE: The present study was designed to determine the toxicity and maximum 
      tolerated doses of oral intermittent oral capecitabine and subcutaneous (s.c.) 
      rHuIFNalpha2a in patients with metastatic renal cell carcinoma (RCC). The 
      pharmacokinetics of capecitabine and its metabolites were also investigated. 
      METHODS: A total of 27 patients were treated at four dose levels of capecitabine 
      (825 or 1000 mg/m2 twice daily orally, days 1-14, 22-36) and rHuIFNalpha2a (1.5 
      or 3.0 MU/m2 s.c. three times weekly). Unchanged capecitabine and its metabolites 
      were analyzed in plasma using liquid chroatography/mass spectrometry in ten 
      patients. RESULTS: The toxicity of combined capecitabine and rHuIFNalpha2a was 
      moderate. Patients experienced mild nausea/vomiting (70%) and diarrhea (63%). The 
      hand-foot syndrome was seen in 67% of patients and was generally mild, as was 
      hematologic toxicity. Dose-limiting toxicity included diarrhea, mucositis, 
      neutropenia and the hand-foot syndrome. The dose level recommended for further 
      trials included capecitabine 1000 mg/m2 twice daily and rHuIFNalpha2a 3.0 MU/m2 
      three times weekly. One patient had a partial response of a liver lesion 
      (duration > 200 days). Pharmacokinetic parameters of capecitabine and its 
      metabolites (5'-deoxy-5-fluorouridine, 5-fluorouracil and 
      alpha-fluoro-beta-alanine) were similar to those reported by other authors. There 
      was rapid conversion to 5'-deoxyuridine. The peak plasma concentrations of 
      capecitabine occurred between 0.5 and 3.0 h. CONCLUSIONS: The combination of 
      capecitabine and rHuIFNalpha2a was well tolerated. The recommended dose levels 
      for phase II trials are: rHuIFNalpha2a 3.0 MU/m2 s.c. three times weekly and oral 
      capecitabine 1000 mg/m2 twice daily for 2 weeks. No evidence of an effect of 
      rHuIFNalpha2a on the pharmacokinetics of capecitabine or its metabolites was 
      apparent. A phase II trial in untreated patients with metastatic RCC is planned.
FAU - Chang, D Z
AU  - Chang DZ
AD  - Experimental Therapeutics Program, Cleveland Clinic Taussig Cancer Center, OH 
      44195, USA.
FAU - Olencki, T
AU  - Olencki T
FAU - Budd, G T
AU  - Budd GT
FAU - Peereboom, D
AU  - Peereboom D
FAU - Ganapathi, R
AU  - Ganapathi R
FAU - Osterwalder, B
AU  - Osterwalder B
FAU - Bukowski, R
AU  - Bukowski R
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Interferon-alpha)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Capecitabine
MH  - Chromatography, Liquid
MH  - Deoxycytidine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Diarrhea/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Fluorouracil/analogs & derivatives
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Interferon-alpha/administration & dosage/adverse effects/pharmacokinetics
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Mass Spectrometry
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/drug therapy
MH  - Neutropenia/chemically induced
MH  - Peripheral Nervous System Diseases/chemically induced
EDAT- 2002/01/22 10:00
MHDA- 2002/01/31 10:01
CRDT- 2002/01/22 10:00
PHST- 2002/01/22 10:00 [pubmed]
PHST- 2002/01/31 10:01 [medline]
PHST- 2002/01/22 10:00 [entrez]
AID - 10.1007/s002800100366 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2001 Dec;48(6):493-8. doi: 10.1007/s002800100366.