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.
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 cancerpatients. 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.
Authors: Giulio Francia; Yuval Shaked; Kae Hashimoto; John Sun; Melissa Yin; Carolyn Cesta; Ping Xu; Shan Man; Christina Hackl; Julie Stewart; Mark Uhlik; Anne H Dantzig; F Stuart Foster; Robert S Kerbel Journal: Mol Cancer Ther Date: 2011-12-21 Impact factor: 6.261
Authors: Sandrine J Faivre; Anthony J Olszanski; Karin Weigang-Köhler; Hanno Riess; Roger B Cohen; Xuejing Wang; Scott P Myrand; Enaksha R Wickremsinhe; Candice L Horn; Haojun Ouyang; Sophie Callies; Karim A Benhadji; Eric Raymond Journal: Invest New Drugs Date: 2015-09-16 Impact factor: 3.850