A pilot study of individualized maximum repeatable dose (iMRD), a new dose finding system, of weekly gemcitabine for patients wi

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Pancreas. 2005 Apr;30(3):206-10.

A
pilot study of individualized maximum repeatable dose (iMRD), a new
dose finding system, of weekly gemcitabine for patients with metastatic
pancreas cancer.

Takahashi Y, Mai M, Sawabu N, Nishioka K.
Department of Surgical Oncology, Cancer Research Institute, Kanazawa University, Japan.

OBJECTIVES:
We developed and established a new dose-finding system, the
individualized maximum repeatable dose (iMRD), suitable to induce
prolonged TTP rather than tumor shrinkage.
METHODS: We applied this
system in weekly gemcitabine therapy for 18 metastatic pancreas cancer
patients. We determined the iMRD at the 5th week, after weekly dose
adjustments. We started at 500 mg/m2 (1/2 maximum tolerated dose) of
gemcitabine and repeated the treatment with an increase or a decrease
of 100 mg/m each week, if toxicity was 0 or more than grade 1,
respectively.
RESULTS: The iMRD of weekly gemcitabine was 300 mg/m2 in
2 patients, 400 mg/m2 in 3 patients, 500 mg/m2 in 5 patients, 600 mg/m2
in 6 patients, and 700 mg/m2 in 2 patients, demonstrating significant
differences among individual patients. Grade 3 marrow depression
occurred in only 1 patient (5.6%). Of these 18 patients, 3 (16.7%), 13
(72.2%) and 2 (11.1%) patients showed partial response, stable disease,
and progressive disease, respectively. The median of times to
progressive disease and survival were 4.5 and 9.5 months, respectively.
There were no significant differences in 1-year survival time and more
than 50% reduction rate of serum CA19-9, a tumor marker for pancreatic
cancer, between patients with lower (500 mg/m2 or less) and higher (600
mg/m2 or more) iMRD.
CONCLUSION: These results suggest that iMRD is a
simple method to determine an individual's tailored dose for
chemotherapy and could be the optimal dose for patients with noncurable
cancers such as metastatic pancreas cancer.