Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Comparative cardiac toxicity in two treatment schedules of 5-FU/LV for colorectal carcinoma

The purpose of the study is evaluation and assessment of parameters of cardiac toxicity in patients subjected to 5-FU based chemotherapy. Cardiac morbidity is a reported outcome in different 5FU/LV regimens; however none of them are definite or proximate. The bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective as compared to the monthly regimen of low dose leucovorin. We report the detailed assessment of few cardiac parameter of toxicity in patients of advanced colorectal carcinoma subjected to two Schedules of high and low dose Folinic Acid, 5-Fluorouracil, bolus and continuous infusion. The correlation of elevated cardiac biomarkers, angina and hypertension is comparatively assessed in patients with normal general status, hyperglycemia and known cardiac disorders subjected to two different 5FU based chemotherapeutic regimen

FOLFOX (oxaliplatin and 5fluorouracil/leucovorin) in patients with untreated metastatic gastric adenocarcinoma Phase II study.

Background: Oxaliplatin has shown promising activity in metastatic gastric cancer (MGC) and has synergism with 5 fluorouracil. This phase II study was performed to evaluate the efficacy and safety of FOLFOX4 regimen in MGC. Materials and Methods: Patients with MGC, aged 18-70 years, performance status ≤2, no prior chemotherapy, received FOLFOX4 regimen every 2 weeks as oxaliplatin 85 mg/m 2 IV infusion on day 1 and leucovorin 200 mg/m 2 IV infusion followed by fluorouracil 400 mg/m 2 IV bolus and 600 mg/m 2 22-hour continuous infusion on days 1 and 2. Treatment was administered until progression, unacceptable toxicity, patient's refusal or for a maximum of 12 cycles. Results: From August 2007 to June 2010, 34 patients were prospectively enrolled. The median age was 52 years (28-69). In total, 293 cycles were administered with a median of 8 cycles per patient (range 1-12 cycles) and 33 of 34 patients were assessable for treatment response. The overall response rate were 53% with one patient(3%) had complete response, 17 patients (50%) had partial responses and 6 patients (18%) had stable disease. The median survival of all patients was 12.1 months and the median time to progression was 9.4 months. The most common grade 3/4 toxic effects were neutropenia in four patients (12%), diarrhea in three patients (9%), vomiting in two patients (6%) and peripheral neuropathy occurred in three patients (9%). Conclusions: The FOLFOX4 combination chemotherapy showed a very promising antitumor activity and was generally well-tolerated as a first-line treatment of patients with MGC.

Interstitial Lung Disease Associated with Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin / 대한소화기학회지

Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here.

Interstitial Lung Disease Associated with Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin / 대한소화기학회지

Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here.

Tratamiento con radioterapia y quimioterapia: en pacientes con carcinoma de recto 10 años de evaluación / Treatment with radiotherapy and chemotherapy in patients with rectal carcinoma 10 years of evaluation

Analizar el resultado del tratamiento con radioterapia y quimioterapia con carcinoma rectal evaluando tolerancia, toxicidad, patrón de recurrencia y sobrevida. Se incluyeron 50 pacientes con carcinoma de recto. De ellos 33 recibieron tratamiento posoperatorio y 17 preoperatorio. El 64 por ciento recibió radioterapia a pelvis, 4500- 5540 cGy con fracciones de 180 cGy diarios durante 5-6 semanas concurrente con 5-Fluorouracilo 225 mg/m² en infusión contínua y 36 por ciento 5-Fluorouracilo en bolus con bajas dosis de leucovorina por 5 días consecutivos la primera y la cuarta semana de radioterapia. Las toxicidades grado 3 y 4 más fecuentes con 5-Fluorouracilo en infusión continua concurrente con radioterapia fueron diarrea y enteritis; en los tratados con 5-Fluorouracilo en bolus y leucovorina concurrente con radioterapia fueron diarrea, radiodermatitis y neutropenia. No hubo muertes asociadas al tratamiento. La mayoría de los pacientes eran estadio III. Al 60 por ciento se les realizó una resección anterior de recto. El porcentaje de recaídas locales fue 12 por ciento y a distancia 24 por ciento. Para el momento del análisis el 42 por ciento de los pacientes se encontraban vivos sin enfermedad. Las toxicidades más frecuentes fueron diarrea y enteritis. Se observó mayor toxicidad hematológica (neutropenia grado 3) en el grupo que recibió 5-Fluorouracilo en bolus más leucovorina. La recurrencia local fue similar a la presentada en la literatura con regímenes del tratamiento similares. La principal causa de falla del tratamiento fue la recaída a distancia.

To analyze the results of concurrent radiotherapy and chemotherapy in patients with rectal cancer, and evaluating the treatment tolerance, recurrence pattern, toxicity and survival. 50 patients with rectal carcinoma were included. 33 were treated postoperatively and 17 preoperatively. The 64 % received radiotherapy to the pelvis, 4500-5540 cGy for 5 to 6 weeks with daily 180 cGy fractions concurrent with 5-Fluorouracil 225 mg/m2 by protracted infusion and 36 % of them received radiotherapy concurrent with bolus 5-Fluorouracil with low dose leucovorin for 5 consecutive days, the first and fourth week of radiotherapy. The most frequent grade 3 and 4 toxicities with protracted infusion of 5-Fluorouracil were diarrhea and enteritis; in patients treated with bolus 5-Fluorouracil and low dose leucovorin diarrhea, radio dermatitis and neutropenia were seen. There were no toxic deaths associated with treatment. The majority of patients had stage III disease. The 60 % of patients underwent anterior rectal resection. The rate of local recurrence was 12 % and distant metastasis 24 %. At the time of the study analysis 42 % of the patients were alive without disease. The most common toxicities were diarrhea and enteritis. We observed more hematological toxicity (grade 3 neutropenia) in the group of patients treated with bolus 5-Fluorouracil and leucovorin. The rate of local recurrence was similar to the published data with the same regimens of treatment and the main cause of treatment failure was distant metastasis.

Nuevas alternativas en el tratamiento del cancer gástrico avanzado / Treatment of advanced gastric cancer with oxaliplatin plus 5-fluorouracil/ leucovorin (FOLFOX-4 chemotherapy)

Background: Chemotherapy improves survival in advanced gastric cancer. However the most active combinations have a high level of toxicity that limits their use. Aim: To assess the response, toxicity and survival of patients with advanced gastric cancer, treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4 chemotherapy). Material and methods: Patients with stage IVgastric cancer, according to the American Joint Committee on Cancer or with relapsed disease and functional capacity 0-2 of the South West Oncology Group, were included. FOLFOX-4 chemotherapy was used as first or second line treatment. The response to treatment and survival were assessed. Results: Between 2003 and 2006, 29 patients (median age 52.5 years, 69 percent males) were treated. FOLFOX-4 was given as first line treatment in 65 percent patients and as second line in 35 percent. There was a complete response in 4.6 percent, partial response in 68 percent, stable disease in 20.6 percent and progression in 6.8 percent. Toxicity was observed in 51 percent of patients, that was hematological and non hematological grade 3/4 in 14 percent. Median survival was 12.5 months. Conclusions: FOLFOX-4 chemotherapy was active in advanced gastric cancer and had a low level of toxicity.

FOLFIRI chemotherapy for metastatic colorectal cancer patients.

OBJECTIVES: 1) To confirm the efficacy of irinotecan plus folinic acid/continuous 5-fluorouracil as bimonthly FOLFIRI regimen in metastatic colorectal cancer patients. Efficacy evaluations will include response rate, duration of response, and survival. 2) To evaluate safety profiles on patients receiving this combination. MATERIAL AND METHOD: Nineteen patients with metastatic colorectal cancer received 180 mg/m2 intravenous (iv) day 1 of irinotecan, 200 mg/m2 iv of folinic acid, 400 mg/m2 iv bolus days 1 to 2, 5-fluorouracil (5-FU), and 600 mg/m2 iv 5-FU infusion over 22 hours, days 1 to 2. Treatment was repeated every two weeks and one cycle contained three fortnightly administrations. Sites of disease were liver in nine patients, lungs in three patients, bowels in four patients, lymph nodes in three patients, and peritoneum in two patients. Two patients had > 1 metastatic site. Previous treatments included adjuvant chemotherapy in seven cases and front-line chemotherapy for advanced disease in one case. RESULTS: A median of six treatment cycles was completed (range, 2-13 cycles). All patients were assessable for toxicity and 16 patients were evaluable for treatment response. The non-hematological toxicity was mild. Most had grade 1 or 2. Only one patient experienced grade 3 fatigue and anorexia, and discontinued chemotherapy after the second cycle. There were no cases with grade 4 toxicity. Fourteen patients had at least grade 2 alopecia. The most common hematological toxicity was neutropenia. Grade 3 and 4 neutropenia were observed in three and two patients, respectively. There was no case of febrile neutropenia. Based on intention to treat analysis, there were no complete responses (CR), five (26.3%) partial response (PR), and 11 (57.9%) stable disease. With the median follow-up of 6.6 months, the median time to disease progression was 4.7 months and the median survival time was 10.6 months. CONCLUSION: Bimonthly irinotecan in combination with folinic acid and 5-fluorouracil was active with acceptable toxicities and a prolonged survival time in pretreated colorectal cancer. Additional trials to define the optimal dose and schedule of treatment are justified.

Response to initial treatment of low and intermediate risk gestational trophoblastic disease with methotrexate and folinic acid.

OBJECTIVES: To evaluate the response and toxicity of methotrexate and folinic acid given as primary treatment of low and intermediate risk gestational trophoblastic disease (GTD). MATERIAL AND METHOD: Medical records review was performed in patients who received methotrexate and folinic acid as a primary treatment of low and intermediate risk persistent GTD between January 1992 and December 2001. Response was defined as decline of beta human chorionic gonadotropin (hCG) to < or = 5 mlU/ml (remission) after methotrexate and folinic acid treatment. Response rate was estimated and factors associated with response were evaluated. RESULTS: Ninety four eligible patients were treated with intramuscular methotrexate and folinic acid. Complete remission was achieved in 64 cases (68%, 95% CI 58-78%). Mucositis (6.4%) and hepatotoxicity (6.4%) were the most common toxicity of methotrexate in the present study and none of these toxic effects was life threatening. Factors associated with response were initial serum hCG < or = 10,000 mlU/ml and stage I disease. CONCLUSION: Methotrexate with folinic acid is effective treatment for low and intermediate risk GTD with minimal severe toxicity.

Tratamiento médico de 44 pacientes con carcinoma del conducto anal / Medical treatment of 44 patients with anal canal carcinoma

Con el objeto de investigar el tratamiento médico del carcinoma del conducto anal (CAA), 27 pacientes fueron tratados con cisplatino, fluorouracilo y radioterapia en un esquema alternante; 11 pacientes recibieron mitomicina C en lugar del platino,m y 6 pacientes ingresaron a un nuevo protocolo ambulatorio con cisplatino, fluorouracilo, leucovorina y mitomicina C asociado a radioterapia concurrente. Con el primer esquema llegaron a respuesta completa 18/25 pacientes evaluables, y todos se mantienen libres de enfermedad hasta la fecha. Con el segundo plan, 7/10 pacientes evaluables lograron respuesta completa y 5 están vivos, libres de enfermedad. Finalmente con el último plan, 6/6 pacientes ingresados obtuvieron respuesta completa. Nuestra experiencia es una de las primeras en estudiar la utildiad del cisplatino como droga de primera línea en el tratamiento no quirúrgico del CCA. Creemos que es factible utilizar cisplatino y que su toxicidad no resulta limitante. La efectividad, comparable a la de otros esquemas, puede ser mejorada con la administración concurrente de radioterapia, tal como se observa en el útimo esquema implementado