ABSTRACT
PURPOSE: To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy. PATIENTS AND METHODS: Irinotecan was randomly administered in two different schedules (once every 3 weeks, and every 10 days) in patients failing prior 5-FU plus LV. Patients were randomized to two treatment groups: group A received irinotecan 350 mg/m2 every 21 days and group B received irinotecan 175 mg/m2 days 1 and 10 every 21 days. RESULTS: Group A comprised 60 patients: 34 male/26 female, median age 64 years (range 48-70 years), and median Karnofsky performance status (PS) 90. Their metastatic sites included liver (n=47), lymph nodes (n=27), lung (n=14), abdomen (n=14), pelvis (n=8), "other" (n=2), and local recurrence (n=12). Group B comprised 60 patients: 36 male/24 female, median age 62 years (46-70 years), and median PS 90. Their metastatic sites included liver (n=49), lymph nodes (n=29), lung (n=17), abdomen (n=16), pelvis (n=11), "other" (n=2), and local recurrence (n=13). Group A showed the following responses: complete response (CR) 2, partial response (PR) 12, stable disease (SD) 21, progressive disease (PD) 26, overall response rate (ORR) 23%, tumor growth control 58%. Group B showed the following responses: CR 1, PR 14, SD 22, PD 23; ORR 25%; tumor growth control 62%. Toxicities included acute cholinergic syndrome (group A 53%, group B 19%; P<0.0001), late-onset diarrhea grade 1/2 (group A 21%, group B 46%) and grade 3/4 (group A 41%, group B 66%; P<0.0001), nausea and vomiting grade 1/2 (group A 34%, group B 59%) and grade 3/4 (group A 30%, group B 12%; P<0.0001), neutropenia grade 3/4 (group A 27%, group B 28%; P<0.03), with febrile neutropenia seen in only four patients in group A, anemia grade more than 2 (group A 28%, group B 12%; P<0.05), asthenia grade more than 3 (group A 24%, group B 18%; P<0.001), and alopecia grade more than 3 (group A 40%, group B 34%; P<0.2). CONCLUSIONS: . The present study indicates that, in patients with ACC who have relapsed after 5-FU plus LV, the administration of irinotecan fractionated into two doses every 21 days yields a similar efficacy to, but a much lower incidence of toxicity than, the same total dose of irinotecan administered once every 21 days.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Colorectal Neoplasms/drug therapy , Neoplasm Recurrence, Local , Topoisomerase I Inhibitors , Adenocarcinoma/enzymology , Adenocarcinoma/mortality , Aged , Camptothecin/administration & dosage , Camptothecin/adverse effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/enzymology , Colonic Neoplasms/mortality , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/mortality , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Irinotecan , Karnofsky Performance Status , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Metastasis , Rectal Neoplasms/drug therapy , Rectal Neoplasms/enzymology , Rectal Neoplasms/mortalityABSTRACT
The purpose of the present study was to investigate the association between performance status (PS) and mean dose of irinotecan (CPT-11) in patients with recurrent advanced colorectal cancer relapsing after 5-fluorouracil and leucovorin chemotherapy. Patients who had completed their last chemotherapy course with 5-fluorouracil and leucovorin for at least 6 weeks and progressed were included. Based on PS, we administered a starting dose of 250 mg/m(2) in patients with a PS 70-80 (group A), and 350 mg/m(2) for those with a PS > 80 (group B). Of a total of 90 treated patients, all were evaluable, 18 had a partial response (PR) (20%), 39 stable disease (43%), and 15 progressed (37%). No significant difference was noticed between patients with PS > or = 90 or < or = 80 (p = 0.925), or between those who received a mean dose of CPT-11 > or = 300 or < or = 300 (p = 0.602), for response, survival and time to progression. Toxicity was increased in group B as expected, with significant differences for acute cholinergic syndrome (p = 0.02), diarrhea after the first 24 h (p = 0.03) and severe diarrhea (p = 0.03). According to these results, we conclude that response to CPT-11 is independent of its dose, and that a dose of 250 mg/m(2) every 3 weeks might be a cost-effective and less toxic alternative in this setting. However, further adequately powered phase II or III randomized studies might be required in order to confirm this observation.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camptothecin/pharmacology , Colonic Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Colonic Neoplasms/pathology , Cost-Benefit Analysis , Drug Costs , Drug Resistance, Neoplasm , Female , Fluorouracil/administration & dosage , Fluorouracil/pharmacology , Health Status , Humans , Irinotecan , Leucovorin/administration & dosage , Leucovorin/pharmacology , Male , Middle Aged , Treatment OutcomeABSTRACT
Mesenchymal hamartoma of the liver is an unusual oncologic entity which occurs almost exclusively in infancy and childhood; fewer than 200 cases have been reported. We present the case of a 21-year-old female, who was admitted to our institution with a painful right subcostal mass lasting for 6 months, who had no evidence of generalised disease. Imaging procedures revealed a central solid lesion, 15 cm in diameter, in the right lobe of the liver, with cystic degeneration. The patient underwent a formal right hepatectomy. The pathology report ascertained the presence of a benign mesenchymal hamartoma of the liver.