Resectable locally advanced gastric adenocarcinoma: interim analysis

Background: The MAGIC and ACCORD 07 trials have established the role of perioperative chemotherapy in locally advanced gastric adenocarcinoma. A more recent study has demonstrated the superiority of the FLOT perioperative regimen. The best strategy to improve outcomes has yet to be determined. Aims of the study were to evaluate perioperative chemotherapy in terms of morbidity and tolerance of FLOT regimen with modification and histopathological responseMethods: This prospective study was started after ethical committee approval in February 2019 at a tertiary cancer center in South India for a period of 1 year up till February 2020. Patients fulfilling inclusion criteria were enrolled. Perioperative chemotherapy was given as scheduled regimen and adverse effects and response to preoperative chemotherapy were recorded. Radical D2 gastrectomy and histopathology assessed analysed by using IBM SPSS statistics ver. 21 and descriptive statistics used.Results: From February 2019 till February 2020, a total of 24 patients of newly diagnosed adenocarcinoma of the stomach of which 18 patients were nonmetastatic on workup. Moderately different (38.8%), well-differentiated in 11.2%, poorly differentiated in 50%. Total 66.7% were diagnosed as metastatic on staging laparoscopy, peritoneal wash cytology in 50% was negative. The cardiopulmonary resuscitation was seen in two patients.Conclusions: Even though it is an interim analysis with less number of patients enrolled, so far it can be concluded that all patients where surgery is planned should undergo peritoneal lavage cytology and FLOT regimen can be practised with acceptable morbidity. Long term results after completion of study will definitely throw more light.

Retrospective evaluation and prediction of clearance and toxicity of high dose methotrexate in childhood acute lymphoblastic leukemia patients

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

Efficacy and Safety of Bolus 5-Fluorouracil and L-Leucovorin as Salvage Chemotherapy for Oral Fluoropyrimidine-Resistant Unresectable or Recurrent Gastric Cancer: A Single Center Experience

PURPOSE: The International Organization for Standardization-5fluorouracil (FU) 10 trial found that bolus 5-FU and l-leucovorin was not inferior to S-1 in the treatment of gastric cancer (GC). Continuous 5-FU and the rapid injection of 5-FU have different anti-cancer effects. Thus, bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. MATERIALS AND METHODS: We retrospectively analyzed the medical records of all patients with S-1 or capecitabine-resistant, unresectable, or recurrent GC treated with bolus 5-FU and l-leucovorin between January 2010 and December 2015 at Hokkaido University Hospital. The bolus 5-FU and l-leucovorin regimen consisted of intravenous l-leucovorin (250 mg/m²/2 h) and bolus 5-FU (600 mg/m²) administered once weekly followed by a 2-week rest period; each cycle was repeated every 8 weeks. RESULTS: A total of 14 patients were identified. The disease control rate was 35.7%. The median progression-free survival was 1.6 months (95% confidence interval [CI], 1.3~2.0 months), and the median overall survival was 6.3 months (95% CI, 4.7~7.9 months). No patient died from treatment-related causes. The most common severe adverse event associated with bolus 5-FU and l-leucovorin was neutropenia, which occurred in 21.4% of patients. CONCLUSIONS: Bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. We are planning a multi-center prospective phase II trial to evaluate the efficacy and safety of bolus 5-FU and l-leucovorin treatment for pre-treated unresectable or recurrent GC to confirm the results of this limited, retrospective study.

Effects of Rehabilitation Surgery Assisted to FOLFOX Chemotherapy on Postoperative Recovery,Complica-tions and Quality of Life in Patients with Colorectal Cancer / 中国药房

OBJECTIVE:To investigate the effect of rapid rehabilitation surgery assisted to fluorouracil,oxaliplatin,leucovo-rin(FOLFOX)on postoperative recovery,complications and quality of life in patients with colorectal cancer. METHODS:60 pa-tients with colorectal cancer were randomly divided into control group(30 cases)and observation group(30 cases). After resection of colorectal cancer,control group received 85 mg/m2 Oxaliplatin for injection,2 h intravenous infusion,d1+200 mg/m2 Calcium le-vofolinate for injection,intravenous infusion,once a day,d1-2+400 mg/m2 Fluorouracil injection,intravenous infusion,once a day, d1-5 then 600 mg/m2 for 22 h intravenous infusion,d1-2. Observation was additionally given rapid rehabilitation surgery. 2-week was regarded as 1 course,it lasted 12 courses. Urinary retention time,anal exhaust time,first defecation time,postoperative hospital-ization time,scores of life quality (overall health,emotional function,mental health,physiological functions,physical function,so-matic pain,vitality,social function)in 2 groups were observed,and the incidence of postoperative complications was recorded. RE-SULTS:The urinary retention time,anal exhaust time,first defecation time,postoperative hospitalization time in observation group were significantly shorter than control group,the incidence of postoperative complications in observation group was signifi-cantly lower than control group,overall health,emotional function and mental health score were significantly higher than control group,the differences were statistically significant(P0.05). CONCLUSIONS:Rapid rehabilitation sur-gery assisted to FOLFOX chemotherapy can reduce the incidence of postoperative complications in patients with colorectal cancer, improve quality of life,shorten hospitalization time and promote postoperative recovery.

Feasibility of Oxaliplatin, Leucovorin, and 5-Fluorouracil (FOLFOX-4) Chemotherapy in Heavily Pretreated Patients with Recurrent Epithelial Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to evaluate the efficacy and toxicity of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Clinical data were reviewed in 28 patients who received FOLFOX-4 as more than the second-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin as a 2-hour infusion, 200 mg/m2 of leucovorin as a 2-hour infusion, and bolus 400 mg/m2 on day 1, followed by a 22-hour infusion of 600 mg/m2 of 5-fluorouracil for two consecutive days every three weeks. In addition, its efficacy and toxicity were compared with those reported in in three previous relevant studies. RESULTS: A total of 128 cycles of FOLFOX-4 were administered with the median number of five cycles (range, 1 to 10 cycles). In nine patients with measurable disease, complete response (CR) and partial response (PR) were observed in 0 (0%) and two (22.2%) patients, whereas in 19 patients with non-measurable disease, CR and PR were observed in 0 (0%) and five (26.3%) patients. Among all patients, grade 3 anemia, neutropenia, and thrombocytopenia were observed in two (7.1%), three (10.7%), and one (3.6%) patient, and grade 3 fatigue, nausea and vomiting, and peripheral neuropathy were observed in one (3.6%), two (7.1%), and three (10.7%) patients. In addition, median values of time to progressive disease and chemotherapy-specific survival were three months (range, 0 to 10 months) and nine months (range, 4 to 24 months). CONCLUSION: FOLFOX-4 is feasible as salvage chemotherapy with acceptable toxicity for heavily pretreated patients with recurrent EOC.

The efficacy and safety evaluation of 5-FU/LV and FOLFOX4 chemotherapy regimen for colorectal cancer / 中国医师杂志

ObjectiveTo evaluate the efficacy and safety of two different adjuvant chemotherapy regimens of 5-FU/LV and FOLFOX4 in patients who suffered from colorectal cancer after having radical surgery.MethodsBy 123 patient who had colorectal cancer and received radical surgery from December 2005,to May 2007 were enrolled in this using retrospective analysis.68 cases received 5 FU/LV chemotherapy regimens and 35 cases received FOLFOX4 chemotherapy regimens.The results of survival rate and side effects were compared between the two groups.ResultsThe survival rates within 3 years of 5-FU/LV and FOLFOX were 77.3％ and 80％ respectively.There was no significant differences between two chemotherapy regimens ( x2 =1.26,P =0.28).The main side effects included anorexia,nausca/vomiting,alopecia and et al.However there was no significant difference in adverse reactions of two groups ( P ＞0.05 ).Conclusions5-FU/LV and FOLFOX4 were effective and safe chemotherapy regiments for patients with colorectal cancer after having radical surgery,and the side effects were acceptable in these two groups.

Efficacy and Safety of Hepatic Arterial Infusion of Fluorouracil with Leucovorin as Salvage Treatment for Refractory Liver Metastases from Colorectal Cancer

BACKGROUND/AIMS: Limited options remain for patients with metastatic colorectal cancer (CRC) after failure of standard systemic chemotherapy. Readministration of chemotherapeutic agents by hepatic arterial infusion (HAI) has the rationale of providing higher concentrations of chemotherapeutic agents to hepatic metastases. The present study was conducted to evaluate the efficacy and safety of HAI of fluorouracil with leucovorin (HAI 5-FU/LV) for patients with liver metastases from CRC. METHODS: Fourteen patients with liver metastases from CRC who received HAI 5-FU/LV after failure of systemic chemotherapy containing fluorouracil and leucovorin were identified and their medical records were reviewed. RESULTS: Of 10 patients evaluable for response, one partial response, six stable disease, and three progressive disease were reported. Additionally, the overall response and disease control rates were 7% and 50%, respectively. The median time to progression was 4.3 months (range, 2.9 to 5.6), to hepatic progression was 5.8 months (range, 4.7 to 6.9), and to extrahepatic progression was 5.8 months (range, 2.3 to 9.2). No grade 3/4 hematologic toxicities occurred and one case of abdominal pain and two cases of oral mucositis were the only grade 3 nonhematologic toxicities. Catheter-related complications occurred in three patients: one thrombosis, one infection, and one displacement. CONCLUSIONS: HAI 5-FU/LV was well tolerated and showed modest efficacy for patients with liver metastases from refractory CRC. Readministration of previously used chemotherapeutic agents via the hepatic artery could be an effective salvage option and warrants further investigation in a prospective trial.

Clinical study of oxaliplatin combination with calcium folinate and flrorouracil in treatment of advanced esophageal carcinoma / 中国基层医药

Objective To evaluate the efficacy and toxicity of oxaliplatin in combination with calcium folinate and flrDrouracil in treatment of advanced esophageal carcinoma. Methods 61 patients with advanced esophageal cancer were divided into treatment group ( 30 cases) and control group (31 cases). Treatment group was given oxaliplatin combined with calcium folinate and flrorouracil; control group was given cisplatin and calcium folinate and flrorouracil. Results The overall response rate was 43.3% in the treatment group and 41.9% in control group(P＞0.05).The median time to progression( TTP) was 8.1 months vs.7.9 months(P＞0.05).Compared with control group,the treatment group, the side effects of myelosuppression, stomasitis and alopecia were not significant difference (P ＞ 0. 05 ) , grade Ⅰ -Ⅳ nausea and vomiting( P = 0. 028 ) , diarrhea (P = 0. 039 ) and renal toxicity ( P = 0.044 ) were lower,while the peripheral nerve toxicity ( P = 0. 010) was higher. Conclusion The effect of oxaliplatin combined with calcium folinate and flrorouracil had satisfactory effect in the treatment of advanced esophageal carcinoma, and the poisonous side effect was low. It could be used as first-line chemotherapy regimen.

A comparison of vitamin A and leucovorin for the prevention of methotrexate-induced micronuclei production in rat bone marrow

INTRODUCTION: Methotrexate, a folate antagonist, is a mainstay treatment for childhood acute lymphoblastic leukemia. It is also widely used in a low dose formulation to treat patients with rheumatoid arthritis. In rats, methotrexate is known to induce micronuclei formation, leading to genetic damage, while vitamin A is known to protect against such methotrexate-induced genetic damage. Leucovorin (folinic acid) is generally administered with methotrexate to decrease methotrexate-induced toxicity. OBJECTIVES: We aimed to determine whether vitamin A and leucovorin differed in their capacity to prevent formation of methotrexate-induced micronuclei in rat bone marrow erythrocytes. The present study also aimed to evaluate the effect of combined treatment with vitamin A and leucovorin on the formation of methotrexate-induced micronuclei. METHODS: Male and female Wistar rats (n=8) were injected with 20 mg/kg methotrexate (single i.p. dose). The control group received an equal volume of distilled water. The third and fourth groups of rats received vitamin A (5000 IU daily dose for 4 successive days) and leucovorin (0.5 mg/kg i.p. dose for 4 successive days), respectively. The fifth and sixth groups of rats received a combination of vitamin A and a single dose of methotrexate and a combination of leucovorin and methotrexate, respectively. The last group of rats received a combination of leucovorin, vitamin A and single dose of methotrexate. Samples were collected at 24 hours after the last dose of the treatment into 5 percent bovine albumin. Smears were obtained and stained with May-Grunwald and Giemsa. One thousand polychromatic erythrocytes were counted per animal for the presence of micronuclei and the percentage of polychromatic erythrocyte was determined. RESULTS: Comparison of methotrexate-treated rats with the control group showed a significant increase in the percentage of cells with micronuclei and a significant decrease polychromatic...

Clinical Efficacy of CPT-11 Combined with 5-Fu/LV Regimen for Advanced Colorectal Cancer / 中国药房

OBJECTIVE: To observe the clinical efficacy and toxic effects of irinotecan (CPT-11) combined with 5-fluorouracil/leucovorin (5-Fu/LV) in the treatment of advanced colorectal cancer. METHODS: Among 31 cases of advanced colorectal cancer, 30 cases were evaluable. All patients received 2 weeks of therapy regimen: CPT-11 180 mg?m-2 i.v. gtt d1, LV 200 mg?m-2 i.v. gtt d1～2, 5-Fu 400 mg?m-2 i.v. and 5-Fu 600 mg?m-2 i.v. gtt for 22 h, d1～2. A treatment course last for 14 days. 6 weeks later, clinical efficacy was evaluated. RESULTS: Complete remission was observed in 1 case and partial remission 11 cases. The remission rate (RR) was 40%. Stable disease was reported in 14 cases and disease progression 4 cases. Medium time to progress (TTP) was 6.5 months and medium survival time(MST) was 13.9 months. Major toxic reactions were delayed diarrhea (Ⅲ/Ⅳ grade of 30%) and neutropenia (Ⅲ/Ⅳ grade of 26.6%). CONCLUSION: The regimens of CPT-11 combined with 5-Fu / LV have high response rate and tolerable toxicity in treatment of advanced colorectal cancer. It can be use as first or second line chemotherapy for advanced colorectal cancer.

Diffuse alveolar damage during chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin / 대한내과학회지

The combination chemotherapy of oxaliplatin with 5-fluorouracil and leucovorin (FOLFOX regimen) has been recently proved to be beneficial in advanced colorectal and gastric cancer. Side effects of this regimen include neutropenia, diarrhea, and neurosensory toxicity. However, the case reports about pulmonary toxicities of this regimen are very limited. Herein is the reported case of a patient treated with oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in whom diffuse alveolar damage developed and the disease improved after steroid pulse therapy.

Phase II Study of Oxaliplatin, 5-fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as Second Line Therapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of the study was to assess the efficacy and safety of biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic colorectal cancer (CRC) as a second line therapy. MATERIALS AND METHODS: Between November 2002 and October 2005, 26 patients with histologically confirmed relapsed or metastatic CRC were enrolled. All patients were previously treated with irinotecan-based combination chemotherapy. The chemotherapy regimen consisted of oxaliplatin 85 mg/m2 on day 1; LV 200 mg/m2 on days 1 and 2; and 5-FU 400 mg/m2 bolus IV with 600 mg/m2 with a 22-hour infusion on days 1 and 2 every 2 weeks. RESULTS: The median age of the 26 patients was 50.5 years (range, 31~72). Their metastatic sites included: the liver (42.3%), peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were evaluated for their response. Four patients achieved partial responses and 15 patients had stable disease. The overall response rate was 16% (95% confidence interval; 1.7~30.3%). The median follow-up duration for the surviving patients was 7.4 months (range, 2.08~21.2). Median overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%, respectively. The most common hematological toxicities were: NCI grade I/II leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%). The main non-hematological toxicities were: grade I/II peripheral neuropathy (16.1% and 21.5%, respectively) and nausea/ vomiting (23.6%/18.5%). There was no life-threatening toxicity. CONCLUSION: The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or metastatic colorectal cancer patients as second line chemotherapy.

A Phase II Study of Irinotecan, 5-Fluorouracil and Leucovorin for Treatment in Patients with Previously Untreated Advanced Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We prospectively conducted a non-randomized phase II trial to evaluate the efficacy and safety of combination irinotecan, leucovorin (LV) and 5-fluorouracil (FU) as a first-line regimen for treating patients with previously untreated advanced colorectal cancer (CRC). MATERIALS AND METHODS: Twenty-six previously untreated patients with advanced, recurrent or metastatic CRC were enrolled in this study. The patients received either irinotecan 180 mg/m2 on day 1 with LV bolus of 200 mg/m2 and FU bolus of 400 mg/m2, and this was followed by FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the FOLFIRI regimen), or they were treated with LV bolus of 400 mg/m2 and FU bolus of 400 mg/m2 followed by FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. RESULTS: The objective response rate was 23.1% (6/26) respectively, for both treatments. The median time to progression was 5.3 months (range: 0.4~19.9), and the overall survival was 11.2 months (range: 0.5~52.3). The prognostic factor for longer survival was the Eastern Cooperative Oncology Group (ECOG) performance status (PS). The non-hematological toxicities were similar for both treatment groups, with more frequent grade > or =3 neutropenia being noted for the simplified FOLFIRI regimen. CONCLUSION: The biweekly irinotecan based regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and the ECOG PS was the independent prognostic factor.

Clinical Observision of Semimonthly Regimen for Paclitaxel Combined with 5-fluorouracil/leucovorin 48-hour Continuouse Infusion in Treatment of Advanced Breast Cancer Which Resistence CAF Regimen / 医学研究杂志

Objective To study the clinical application value of advanced breast cancer which resistence CAF regimen,treated with semimonthly regimen for paclitaxel combined with 5-fluorouracil/leucovorin 48-hour continuouse infusion.Methods 80 paients with CAF-regimen-resistant ABC were treated with paclitaxel combined with 5-fluorouracil/leucovorin continuouse infusion,paclitaxel 95mg/m2,d_1,LV 200mg,d_1,5-fluorouracil 3g/m2,continuouse infusion for 48 hours with infusion pump.every cycle lasted 2 weeks,at least 4 cycles.Results Of 80 patients,there were 9 complete and 26 partial responses,32 cases remained stable and 13 progressive.The overall response rate of 43.8%.The median time to progression was 8 months.The median survival time was 16.7 months,the patients with soft tissue,lung,pleura,bone,liver obtained response rat was 46.7%(21/45),38.5%(5/13),31.3%(5/16),40%(4/10),20%(2/10).Conclusions semimonthly regimen for paclitaxel combined with 5-fluorouracil/leucovorin 48-hour continuouse infusion is effective and acceptable toxicity,it could be considered as one of the standard chemotherapy for advanced breast cancer which resistence CAF regimen.

Feasibility of Leucovorin Rescue Guided with Methotrexate Plasma Concentration / 实用儿科临床杂志

Objective To evaluate the feasibility of leucovorin(LCV) rescue protocol defined by us,we compared the plasma concentrations,toxicity,LCV doses of different high doses methotrexate(HD-MTX).Methods Seventeen children with acute lymphoblastic leukemia and 1 children with non-Hodgkin′s lymphoma were randomly treated with total 43 courses of HD-MTX.MTX plasma concentrations were measured by fluorescence polarization immuno-assay.Different LCV rescue protocols were prospectively defined for 3 kinds of HD-MTX protocols.Adjusting LCV dose by plasma MTX concentrations.Results No irreversible MTX-related toxicity was observed in all patients.Significant differences of mean steady-state plasma concentrations(Cpss) and total rescue doses were found between 3 groups(P

Pulmonary Fibrosis Under Chemotherapy with Oxaliplatin, 5-fluorouracil, and Leucovorin / 결핵및호흡기질환

The combination of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) has recently been shown to be beneficial in advanced colorectal and gastric cancers. The side effects of this regimen include neutropenia, diarrhea and neurosensory toxicity. However, case reports on the pulmonary toxicities of this regimen are very limited. Especially, the development of pulmonary fibrosis has never been cited in the literature. Herein is reported the case of a patient treated with oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in whom pulmonary fibrosis developed, but which improved after steroid pulse therapy.

Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer

BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. METHODS: Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastatic colorectal cancer were enrolled. The chemotherapy regimen schedule consisted of 180 mg/m2 of irinotecan being administered intravenously (i.v) on Day 1, 400 mg/m2 of 5-FU via i.v bolus with 600 mg/m2 of continuous infusion for 22 hrs on both Day 1 and 2, and 20 mg/m2 of leucovorin on both Day 1 and 2, repeated every two weeks. RESULTS: The overall response rate was 47.8%. Of the 40 evaluated patients, one had CR (2.3%) and 20 had PR (46.5%). Toxicities were mild and easily manageable. Three patients experienced 23 episodes of Grade 3/4 leukopenia., Only one patient developed Grade 3/4 diarrhea. None experienced Grade 3/4 thrombocytopenia. CONCLUSION: Modified FOLFIRI with a low dose of LV is an effective and tolerable regimen for patients with recurrent or metastatic colorectal cancer.

Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to evaluate the efficacy and tolerability of the oxaliplatin, 5-fluorouracil (5-FU) and low dose leucovorin (LV) combination in patients with advanced colorectal cancer. MATERIALS AND METHODS: Patients with unresectable or recurrent colorectal carcinomas were prospectively accrued. Up to one prior chemotherapy regimen was allowed. Patients received oxaliplatin, 85 mg/m2, administered as a 2-hour infusion on day 1, followed by LV, 20 mg/m2, as a bolus and 5-FU, 1, 500 mg/m2, via continuous infusion for 24 hours on days 1 and 2. Treatment was repeated every 2 weeks until disease progression or adverse effects prohibited further therapy. RESULTS: Between August 1999 and May 2004, 31 patients were enrolled in this study. Of the patients enrolled, 24 and 31 were evaluable for tumor response and survival analysis, respectively. The patients' characteristics included a median age of 59, with 6 (19%) having had prior chemotherapy. No patient achieved a complete response, but nine (38%) attained a partial response. Seven (29%) patients maintained a stable disease and 8 (33%) experienced increasing disease. The median duration of the response was 6 months. After a median follow-up of 9.6 months, the median time to progression was 3.8 months, with a median survival of 10.7 months. The hematological toxicities were mild to moderate, with no treatment-related mortality or infection. The major non-hematological toxicity was gastrointestinal toxicity. CONCLUSIONS: The combination chemotherapy of oxaliplatin, low dose LV and continuous infusion of 5-FU is safe and has a cost-benefit, but is a moderately effective regimen in advanced colorectal cancer. A randomized trial comparing low and high dosages of leucovorin in the FOLFOX regimen is warranted.

Carboxypeptidase-G2 Rescue in a Patient with High Dose Methotrexate-induced Nephrotoxicity / Journal of the Korean Cancer Association, 대한암학회지

A 13 year-old girl with osteosarcoma and pulmonary tumor recurrence developed acute renal failure following high dose methotrexate (12 g/m2) therapy, she had previously tolerated high dose methotrexate and her renal and hepatic functions were normal. Briefly, 48 hours after beginning methotrexate infusion her methotrexate concentration and creatinine level were 1338.8microM/L and 5.8 mg/dl, respectively. Grade IV oral mucositis and neutropenia with fever developed at 144 hours after MTX infusion. Hydration and alkalinization were continued and leucovorin rescue was intensified based on the plasma MTX concentrations. Plasma exchange was performed twice and hemodialysis 3 times without problems, but methotraxate and creatinine levels remained high, 91.9 microM/L, and 2.5 mg/dl, respectively. After 3 courses of hemodialysis carboxypeptidase-G2 (CPDG2) was administered at 50 U/kg, intravenously over 5 minutes. After 15 minutes of CPDG2 (Voraxaze(TM)) infusion, her plasma MTX concentration was 0.91microM/L and no rebound elevation or side effects developed. Thirteen days post-MTX infusion her renal function had normalized. We report here our experience of a dramatic methotrexate level reduction caused by CPDG2 administration.

The Efficacy of a Modified Chronomodulated Infusion of Oxaliplatin, 5-Fluorouracil and Leucovorin in Advanced Colorectal Cancer (Preliminary Data) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the efficacy and tolerability of a modified chronomodulated infusion of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in the treatment of advanced colorectal cancer. MATERIALS AND METHODS: Sixteen patients with relapsed or metastatic colorectal cancer were treated with an intravenous infusion of oxaliplatin 25 mg/m(2), 5-FU 700 mg/m(2) and leucovorin 20 mg/m(2) on days 1 to 5. The infusion of oxaliplatin was chronomodulated with a peak delivery rate at 16: 00 p.m., with 5-FU infused constantly overnight. Each course was repeated every 21 days. RESULTS: The response rate was 38.5% (95% confidence interval [CI], 13.9% to 68.4%) in the 13 measurable patients, including 1 complete response (7.7%) and 4 partial responses (30.8%). Five patients (38.5%) had a stable disease and 3 (23.0%) a progressive disease. Three patients without a measurable lesion had improved status. The median time to progression and overall survival were 29 weeks and 85 weeks, respectively. Grade 3 thrombocytopenia occurred in 2.5% (2 cycles) and grade 3 vomiting in 12.5% (2 patients). Anorexia, stomatitis, diarrhea, pruritus, alopecia and peripheral neuropathy were mild and tolerable. CONCLUSION: The modified chronomodulated infusion of oxaliplatin, 5-FU and leucovorin is effective and tolerable, but the number of patients was too small. Further study will be needed to confirm the efficacy of this regimen with a larger population of patients.