TY - JOUR
T1 - Phase I trial of intraperitoneal gemcitabine in the treatment of advanced malignancies primarily confined to the peritoneal cavity
AU - Morgan, Robert J.
AU - Synold, Timothy W.
AU - Xi, Bixin
AU - Lim, Dean
AU - Shibata, Stephen
AU - Margolin, Kim
AU - Schwarz, Roderich E.
AU - Leong, Lucille
AU - Somlo, George
AU - Twardowski, Przemyslaw
AU - Yen, Yun
AU - Chow, Warren
AU - Tetef, Merry
AU - Lin, Paul
AU - Paz, Benjamin
AU - Koczywas, Mariana
AU - Wagman, Lawrence
AU - Chu, David
AU - Frankel, Paul
AU - Stalter, Susan
AU - Doroshow, James H.
PY - 2007/2/15
Y1 - 2007/2/15
N2 - Purpose: To determine the maximally tolerated dose, toxicity, and pharmacokinetics of i.p. gemcitabine. Experimental Design: Patients had peritoneal carcinomatosis. Gemcitabine (40, 80, 120, or 160 mg/m2) was administered into the peritoneal cavity in 2 L of warmed saline on days 1, 4, 8, and 12 of a 28-day cycle. Results: Thirty patients received 63 (median, 2; range, 0-6) courses. Tumors included ovary (14), uterus (2), colon (6), pancreas (3), and others (5). Dose-limiting toxicity included nausea, vomiting, diarrhea, dyspnea, fatal respiratory failure, and grade 3 elevation of alanine aminotransferase in three patients. Hematologic toxicity and pain were ≤grade 2. Three patients had decreased or resolved ascites. Of 19 patients evaluable for response, 10 had stable disease (median, 3.5 courses) and 9 had progressive disease. The median peak peritoneal concentration was 1,116-fold (range, 456-1,886) higher than the peak plasma level. Plasma and peritoneal levels were undetectable within 8 to 12 h. At 120 mg/m2, the median peritoneal area under the concentration versus time curve (AUC) was 82,612 ng/mL x h (range, 53,296-199,830) and the plasma AUC was 231 ng/mL x h (range, 47.6-259.5). The mean peritoneal advantage (AUCperitoneal/AUC plasma) was 847 (range, 356-1,385). Conclusions: I.p. administration of gemcitabine is tolerated within the tested dosage range. Technical problems with the Porta-Cath device and i.p. therapy per se may have been exacerbated by the enrollment of many patients with a variety of advanced i.p. diseases. Given the significant increase in local dose intensity and the documented activity of this drug, this agent may be an excellent candidate for i.p. therapy in optimally debulked ovarian cancer, either alone or in combination.
AB - Purpose: To determine the maximally tolerated dose, toxicity, and pharmacokinetics of i.p. gemcitabine. Experimental Design: Patients had peritoneal carcinomatosis. Gemcitabine (40, 80, 120, or 160 mg/m2) was administered into the peritoneal cavity in 2 L of warmed saline on days 1, 4, 8, and 12 of a 28-day cycle. Results: Thirty patients received 63 (median, 2; range, 0-6) courses. Tumors included ovary (14), uterus (2), colon (6), pancreas (3), and others (5). Dose-limiting toxicity included nausea, vomiting, diarrhea, dyspnea, fatal respiratory failure, and grade 3 elevation of alanine aminotransferase in three patients. Hematologic toxicity and pain were ≤grade 2. Three patients had decreased or resolved ascites. Of 19 patients evaluable for response, 10 had stable disease (median, 3.5 courses) and 9 had progressive disease. The median peak peritoneal concentration was 1,116-fold (range, 456-1,886) higher than the peak plasma level. Plasma and peritoneal levels were undetectable within 8 to 12 h. At 120 mg/m2, the median peritoneal area under the concentration versus time curve (AUC) was 82,612 ng/mL x h (range, 53,296-199,830) and the plasma AUC was 231 ng/mL x h (range, 47.6-259.5). The mean peritoneal advantage (AUCperitoneal/AUC plasma) was 847 (range, 356-1,385). Conclusions: I.p. administration of gemcitabine is tolerated within the tested dosage range. Technical problems with the Porta-Cath device and i.p. therapy per se may have been exacerbated by the enrollment of many patients with a variety of advanced i.p. diseases. Given the significant increase in local dose intensity and the documented activity of this drug, this agent may be an excellent candidate for i.p. therapy in optimally debulked ovarian cancer, either alone or in combination.
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U2 - 10.1158/1078-0432.CCR-06-1735
DO - 10.1158/1078-0432.CCR-06-1735
M3 - Article
C2 - 17317834
AN - SCOPUS:33947328024
SN - 1078-0432
VL - 13
SP - 1232
EP - 1237
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -