A phase IB study of the pharmacokinetics of gemcitabine and pemetrexed, when administered in rapid sequence to patients with advanced solid tumors.
BACKGROUND
We have previously demonstrated that pemetrexed is clinically active when administered 90 min after gemcitabine in a phase I study. The present study was undertaken to evaluate the efficacy, toxicity, and pharmacokinetics of gemcitabine and pemetrexed when pemetrexed is administered immediately after gemcitabine.


METHODS
A total of 14 patients received 84 cycles of treatment. Gemcitabine 1250 mg/m(2) was administered on days 1 and 8 of each 21-day cycle, and pemetrexed 500 mg/m(2) on day 8 immediately following gemcitabine administration. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria and recorded as maximum grade per patient for all treatment cycles. Pharmacokinetic analyses of plasma gemcitabine and pemetrexed concentrations were performed.


RESULTS
Neutropenia was the most common severe toxicity. Non-hematologic toxicities, which included nausea, vomiting, fatigue, diarrhea, rash, and elevated transaminases were of mild-to-moderate severity. No increased toxicity was observed with this schedule in comparison to the previous phase I schedule. There was no pharmacokinetic interaction between the two drugs. One partial response was documented in a patient with non-small-cell lung cancer. Eight patients had disease stabilization for five or more cycles.


CONCLUSIONS
Gemcitabine immediately followed by pemetrexed is well tolerated and clinically active, and deserves further evaluation in phase II trials.
Dy
Grace K
GK
Department of Medicine, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Suri
Ajit
A
Reid
Joel M
JM
Sloan
Jeff A
JA
Pitot
Henry C
HC
Alberts
Steven R
SR
Goldberg
Richard M
RM
Atherton
Pamela J
PJ
Hanson
Lorelei J
LJ
Burch
Patrick A
PA
Rubin
Joseph
J
Erlichman
Charles
C
Adjei
Alex A
AA
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine