International Journal of Radiation Oncology*Biology*Physics, 1997
Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation... more Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion !Xuorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. Methods and Materials: Patients with IocalIy advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.&9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m', with dose escalation planned in 25-mg increments, depending on patient tolerance. Results: Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m". One patient experienced Grade 4 anorexia and nausea. No other Grade ~3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5Auorouracil dose of 150 mg/m' daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade z-4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity. Conclusions: In patients with upper-abdominal gastrointestinal cancer, continuous infusion 5Auorouracil(l50 mg/m' daily), leucovorin (10 mg orally daily), aud radiation therapy (50-54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose.
International Journal of Radiation Oncology*Biology*Physics, 1995
Treatment of locally advanced extrapelvic gastrointestinal (GI) cancer, with conventional radiati... more Treatment of locally advanced extrapelvic gastrointestinal (GI) cancer, with conventional radiation therapy (RT) and bolus 5-fluorouracil (5FU) results in only modest prolongation of survival. A recent prospective clinical trial documented ~mproved survival in the adjuvant treatment of rectal cancer with continuous infusion 5FU (OIFU) and RT. In metastatic large bowel cancer, the use of leucovorin as a modulator of 5FU has reaulted in improved response rates and, in sc~me studies, improved survival, in an effort to bu{Id on these results, this prospective multi-institution eIinlca; tria~, was undertaken with the goal of developing a satisfactorily tolerated regimen of RT, CIFU and leucovorin for use in later clinical trials in patients with locally advanced extrapelvic GI cancer. Materials and Melhods: Patients with unresectable, incompletely resected or locally recurrent gaslric, pancreatic, or extrapelvic colon cancer, without distant metastases, whose pedoimance status was 0 or 1 were candidates for this study. RT consisted of 45 Gy in 25 fractions to a field encompassing the primary lumor and regional lymph nodes, followed by 5.4-9 Gy in 3-5 fractions to the tumor (total cumulative dose 50.4-54 Gy). Leucovorin, 10 mg pc daily and CIFU were administered beginning with the first day of RT. CIFU was administered at an initial dose of 125 rag/m2 per day, with subsequent dose escalation in 25 mg increments, depending on patient tolerance. National Cancer Institute Common Toxicity Criteria were used in the assessment of acute adverse effects. Grade 1,2, 3, 4 and 5 corresponded to mild, moderate, severe, life threatening and fatal toxicity respectively. Results: Twenty-four patients participated in this clinical trial. Eight had gastric cancer, 11 had pancreas cancer, 4 had colon cancer and one had a tumor involving both the duodenum and pancreas. Six patients were treated at the initial CIFU dose level of 125 mg/m2 per day. One patient experienced grade 4 anorexia and nausea which required a 2 day hospitalization for intravenous fluids. No other grade 3 or 4 toxicity was observed at this dose level. Eighteen patients were subsequently entered at a planned CIFU dose of 150 rag/m2 per day Three were not evaluable for toxicity at this dose: One patient received an incorrect dose of ClFU. one had toxicity which could nat be distinguished from a preexisting condition, and one received less than haft of the planned course of therapy due to tumor progression Among the remaining 15. ~ experienced grade 3 toxiChy, and zero experienced _> grade 4 toxicity Grade 3 toxicities and the number of patients who developed each were as follow~s: nausea (2 patients), vomiting (3 patients), diarrhea (2 patients), skin (1 patient), hand-foot syndrome (1 patient), catheter related infection (1 patient), and stomatitis (1 patient), Four ot the six patients who experienced grade 3 toxicity developed >1 type of grade 3 toxicity Median survival for the entire group of 24 patients was 8.5 months Median survival among the 12 patients with involvement of the pancreas was 61 months. Conclusion: In patients with upper GI cancer, CIFU (150 rag/m2 per day), leucovorin (10 mg po daily) and RT (50-54 Gy) resulted in a high rate of severe toxicity but no life threatening toxicity among patients who were evaluable for this endpoint. This clinical trial excludes, with 90% confidence, a 20% risk of grade 4 toxicity with this regimen. The rate of severe toxicity suggests that the maximum tolerated dose of CIFU is 150 rag/m2 per day, when used in combination with oral leucovorin and upper abdominal RT. Further clinical trials to test the therapeutic efficacy of this regimen are warranted.
International Journal of Radiation Oncology*Biology*Physics, 1997
Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation... more Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion !Xuorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. Methods and Materials: Patients with IocalIy advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.&9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m', with dose escalation planned in 25-mg increments, depending on patient tolerance. Results: Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m". One patient experienced Grade 4 anorexia and nausea. No other Grade ~3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5Auorouracil dose of 150 mg/m' daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade z-4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity. Conclusions: In patients with upper-abdominal gastrointestinal cancer, continuous infusion 5Auorouracil(l50 mg/m' daily), leucovorin (10 mg orally daily), aud radiation therapy (50-54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose.
International Journal of Radiation Oncology*Biology*Physics, 1995
Treatment of locally advanced extrapelvic gastrointestinal (GI) cancer, with conventional radiati... more Treatment of locally advanced extrapelvic gastrointestinal (GI) cancer, with conventional radiation therapy (RT) and bolus 5-fluorouracil (5FU) results in only modest prolongation of survival. A recent prospective clinical trial documented ~mproved survival in the adjuvant treatment of rectal cancer with continuous infusion 5FU (OIFU) and RT. In metastatic large bowel cancer, the use of leucovorin as a modulator of 5FU has reaulted in improved response rates and, in sc~me studies, improved survival, in an effort to bu{Id on these results, this prospective multi-institution eIinlca; tria~, was undertaken with the goal of developing a satisfactorily tolerated regimen of RT, CIFU and leucovorin for use in later clinical trials in patients with locally advanced extrapelvic GI cancer. Materials and Melhods: Patients with unresectable, incompletely resected or locally recurrent gaslric, pancreatic, or extrapelvic colon cancer, without distant metastases, whose pedoimance status was 0 or 1 were candidates for this study. RT consisted of 45 Gy in 25 fractions to a field encompassing the primary lumor and regional lymph nodes, followed by 5.4-9 Gy in 3-5 fractions to the tumor (total cumulative dose 50.4-54 Gy). Leucovorin, 10 mg pc daily and CIFU were administered beginning with the first day of RT. CIFU was administered at an initial dose of 125 rag/m2 per day, with subsequent dose escalation in 25 mg increments, depending on patient tolerance. National Cancer Institute Common Toxicity Criteria were used in the assessment of acute adverse effects. Grade 1,2, 3, 4 and 5 corresponded to mild, moderate, severe, life threatening and fatal toxicity respectively. Results: Twenty-four patients participated in this clinical trial. Eight had gastric cancer, 11 had pancreas cancer, 4 had colon cancer and one had a tumor involving both the duodenum and pancreas. Six patients were treated at the initial CIFU dose level of 125 mg/m2 per day. One patient experienced grade 4 anorexia and nausea which required a 2 day hospitalization for intravenous fluids. No other grade 3 or 4 toxicity was observed at this dose level. Eighteen patients were subsequently entered at a planned CIFU dose of 150 rag/m2 per day Three were not evaluable for toxicity at this dose: One patient received an incorrect dose of ClFU. one had toxicity which could nat be distinguished from a preexisting condition, and one received less than haft of the planned course of therapy due to tumor progression Among the remaining 15. ~ experienced grade 3 toxiChy, and zero experienced _> grade 4 toxicity Grade 3 toxicities and the number of patients who developed each were as follow~s: nausea (2 patients), vomiting (3 patients), diarrhea (2 patients), skin (1 patient), hand-foot syndrome (1 patient), catheter related infection (1 patient), and stomatitis (1 patient), Four ot the six patients who experienced grade 3 toxicity developed >1 type of grade 3 toxicity Median survival for the entire group of 24 patients was 8.5 months Median survival among the 12 patients with involvement of the pancreas was 61 months. Conclusion: In patients with upper GI cancer, CIFU (150 rag/m2 per day), leucovorin (10 mg po daily) and RT (50-54 Gy) resulted in a high rate of severe toxicity but no life threatening toxicity among patients who were evaluable for this endpoint. This clinical trial excludes, with 90% confidence, a 20% risk of grade 4 toxicity with this regimen. The rate of severe toxicity suggests that the maximum tolerated dose of CIFU is 150 rag/m2 per day, when used in combination with oral leucovorin and upper abdominal RT. Further clinical trials to test the therapeutic efficacy of this regimen are warranted.
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Papers by Roger Santala