Comparative Assessment of Skin and Subcutaneous Toxicity in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

Bano, Nusrat,Najam, Rahila,Mateen, Ahmed Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Objective: The study was designed to assess the skin and subcutaneous toxicity in patients with advanced colorectal carcinoma treated with four different schedules of FOLFOX. Methods: The patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study as per specified inclusion criteria. Toxicity was graded according to CTC v2.0. The frequency of grade 3 and 4 adverse effects were comparatively assessed in each treatment arm. Results: Very severe toxicity was attributed to the FOLFOX7 schedule. The difference between the incidence rate of grade 4 toxicity with all other grades for all parameters of skin and subcutaneous toxicity was highly significant (p=0.00<0.001). Grade 4 hand and foot syndrome was reported only in the FOLFOX7 treatment arm. The most frequent adverse symptom of skin and subcutaneous toxicity reported in the patients treated with modified schedule of FOLFOX was pruritus (grade 1). Frequency and onset of skin and subcutaneous toxic symptoms like alopecia (p=0.000), nail discoloration (p=0.021) and pruritis (p=0.000) was significantly different in each FOLFOX treatment arm. A few cases of oncholysis were also reported in the FOLFOX7 treatment arm. Hand and foot syndrome was fast progressing in patients with grade 1 toxicity. Conclusion: Higher frequency and severity of hand and foot syndrome and pruritus wasa found in the FOLFOX7 treatment arm. Skin and subcutaneous toxicity was comparatively low in the FOLFOX6 treatment arm.

Quality of Life Findings of Adjuvant FOLFOX4 vs. XELOX in Stage III Colon Cancer Patients

Moo In Park,Youn Jung Choi,Seun Ja Park,Won Moon,Sung Eun Kim,Jae Hyun Kim,Byung Kwon Ahn,Sung Uhn Baek,Seung Hyun Lee,Seung Hun Lee Korean Society of Gastrointestinal Cancer 2017 Journal of digestive cancer reports Vol.5 No.2

Background: To compare the quality of life (QoL), the convenience of chemotherapy and satisfaction between colon cancer patients treated with FOLFOX4 and XELOX. Methods: The study was conducted in 26 patients with stage III colon cancer. Patients were received FOLFOX4 (n=17) or XELOX (n=9). QoL, convenience, and satisfaction were assessed using the Quality of Life Questionnaire-C30 (QLQ-C30), Quality of Life Questionnaire-Chemotherapy Induced Peripheral neuropathy (QLQ-CIPN) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at cycle 4 (C4) and cycle 8 (C8) (FOLFOX4) or at cycle 3 (C3) and cycle 6 (C6) visits (XELOX) and at their final visit. Results: In the QLQ-C30, at the final visit, XELOX patients had better functional scores than FOLFOX4 patients (physical: 85.7 vs.60.4, p=0.03; role: 83.3 vs. 57.5, p=0.04) as well as better symptom scores (constipation: 9.5 vs. 40.4, p=0.01). In CIPN, at the C6/C8 visit, XELOX patients had lower motor scale scores than FOLFOX4 patients (3.8 vs. 21.6, p=0.02). Moreover, at the C6/C8 visit, XELOX was more convenient than FOLFOX4 in FACIT-CCSQ (79.7 vs. 55.5, p=0.04). Male patients were especially likely to consider XELOX to be more convenient (90.0 vs. 55.0, p=0.01) and satisfactory (55.4 vs. 26.2, p=0.03) and fewer concern (91.0 vs. 65.0, p=0.03) than FOLFOX4. XELOX patients spent fewer days on hospital visits at C3/C4, C6/C8 and final visit (2.8 vs. 4.2, p=0.01; 2.7 vs. 4.1, p=0.01; 3.0 vs. 4.5, p=0.01). Conclusion: XELOX may be a better adjuvant chemotherapy choice for patients with colon cancer than FOLFOX4 in terms of QoL, convenience, and satisfaction.

Gastrointestinal Adverse Effects in Advanced Colorectal Carcinoma Patients Treated with Different Schedules of FOLFOX

Bano, Nusrat,Najam, Rahila,Qazi, Faaiza,Mateen, Ahmed Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX. Materials and Methods: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared. Results: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin $130mg/m^2$). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin $85mg/m^2$). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin $100mg/m^2$). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05). Conclusions: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm.

진행성 대장암 환자에서 FOLFOX4 복합화학약물 치료의 실패 후 2차 요법으로 FOLFIRI 복합화학약물 치료의 효과와 안전성

김재현 ( Jae Hyun Kim ),박선자 ( Seun Ja Park ),박무인 ( Moo In Park ),문원 ( Won Moon ),김성은 ( Sung Eun Kim ),구기환 ( Ki Hwan Ku ),송성은 ( Sung Eun Song ),김제훈 ( Je Hun Kim ) 대한소화기학회 2014 대한소화기학회지 Vol.63 No.1

Background/Aims: The incidence of colorectal cancer has been increasing every year in Korea. Irinotecan- or oxaliplatin-based regimens including biologic agents are known to be effective in patients with advanced colorectal cancer. But in practice, FOLFOX (combination of oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (combination of irinotecan, 5-fluorouracil, and leucovorin) regimens without biologic agents are more commonly used in Korea due to of the high costs of biologic agents. The aim of this study was to evaluate the efficacy and toxicity of FOLFIRI following FOLFOX4 in patients with advanced colorectal cancer. Methods: A total of 54 patients with advanced colorectal cancer who were treated between May 2005 and May 2013 with FOLFOX4 as first-line chemotherapy and with FOLFIRI as second-line chemotherapy at Kosin University Gospel Hospital (Busan, Korea) were reviewed retrospectively. Results: A total of 54 patients received second-line FOLFIRI chemotherapy. Five patients (9.3%) had a partial response, 29 patients (53.7%) had a stable disease. The median overall survival was 8.90 months and the median time to progression was 4.33 months. Toxicities were tolerable. Conclusions: In a Korean population, FOLFIRI as second-line chemotherapy is effective and well tolerated in patients with advanced colorectal cancer after failure of FOLFOX4. Although the efficacy of FOLFIRI in this study was lower than that of second-line FOLFIRI with biologic agents, these results can help in the formulation of a treatment strategy for financially troubled patients. (Korean J Gastroenterol 2014;63:18-24)

전이성 대장암에서 FOLFOX4 항암 화학요법 시행 중 발생한 간질성 폐질환 1예

윤정석(Jeung-seuk Yoon),박동국(Dong-Guk Park),남궁환(Hwan Namgung),김도형(Doh-hyung Kim) 대한종양외과학회 2012 Korean Journal of Clinical Oncology Vol.8 No.1

Oxaliplatin, 5-Fluorouracil and Leucovorin (FOLFOX-4) as First Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer

Haghighi, Shirin,Kasbkar, Hadi,Esmaeilpour, Keihan,Yasaei, Mehrdad Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

Background: Gastric cancer is considered the fourth most common cancer and second most common cause of cancer-related mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. Aim: To evaluate the responses and complications of FOLFOX-4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. Materials and Methods: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX-4 regimen consisting of a 2h infusion of oxaliplatin $85mg/m^2$ (day 1), continuous infusion of $1000mg/m^2$ 5-Fu in 24h., and leucovorin $200mg/m^2$ in 2h infusion as a first-line chemotherapy. Results: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCI-CTC were seen. Conclusions: The FOLFOX-4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

Adjuvant Chemotherapy Using the FOLFOX Regimen in Colon Cancer

전형준,우진희,이학윤,박기재,최홍조 대한대장항문학회 2011 Annals of Coloproctolgy Vol.27 No.3

Purpose: Great progress has been made in the adjuvant treatment of colon cancer. The aim of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy using the FOLFOX regimen in patients with stage III and high-risk stage II colon cancer. Methods: Eighty-two patients who underwent a potentially curative resection for stage III or high-risk stage II colon cancer were enrolled in this retrospective study. They received FOLFOX4 or modified FOLFOX6. The primary endpoint was disease-free survival. Results: During the median follow-up of 37 months (range, 21 to 61 months), 14 patients experienced disease relapse. The disease-free survival rate at 3 years was 82.9%: 84.6% for stage II and 82.6% for stage III. At the time of the analysis, 8 patients were dead from recurrence. The probability of overall survival at 5 years was 74.5%: 90% for stage II and 74.6% for stage III. Grade 3 or 4 hematologic adverse events included neutropenia (40.2%), anemia (2.4%), and thrombocytopenia (1.2%). Gastrointestinal toxicities included grade 3 or 4 nausea (4.9%) and stomatitis (2.4%). Peripheral sensory neuropathy was observed in 81.7% of the patients during treatment. Of the 11 patients (13.4%) who had grade 3 peripheral sensory neuropathy during treatment, grade 3 symptoms were persistent in 3 patients with gait disturbance at the time of analysis. No treatment-related deaths were recorded. Conclusion: Postoperative chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with stage III and high-risk stage II colon cancer.

위장관 ; 진행성 위암 환자에서 1차 치료 실패 후 2차 요법으로 FOLFIRI 병합화학약물 치료의 효과와 안정성

권혜정 ( Hye Jung Kwon ),박무인 ( Moo In Park ),박선자 ( Seun Ja Park ),문원 ( Won Moon ),김성은 ( Sung Eun Kim ),이혜원 ( Hae Won Lee ),최윤정 ( Youn Jung Choi ),김재현 ( Jae Hyun Kim ) 대한소화기학회 2015 대한소화기학회지 Vol.66 No.1

목적: 수술적 절제가 불가능한 진행성 위암으로 진단된 환자에서 1차 항암요법으로 FOLFOX-4를 시행한 이후 실패하여 2차항암요법으로 irinotecan을 기반으로 한 FOLFIRI 요법을 시행한 환자에서의 효용성과 안정성에 대해 알아보고자 하였다.대상 및 방법: 2005년 9월부터 2012년 2월까지 고신대학교복음병원에 방문하여 절제가 불가능한 진행성 위암으로 진단받고, 1차 항암요법으로 FOLFOX-4를 시행한 이후 치료에 실패하여 2차 항암요법으로 FOLFIRI 요법을 시행한 52명의 환자를 대상으로 후향적으로 시행하였다. 반응은 WHO 기준에근거하여 항암요법 매 3주기마다 시행하였으며, NCI 독성 기준(version 3.0)에 따라 항암요법에 대한 독성을 평가하였다.결과: 대상 환자의 평균연령은 57세였고, 총 생존기간은 7.8개월, 반응 지속기간은 5개월로 조사되었다. 완전 관해는 없었고, 부분 관해가 9예(17.3%), 불변이 30예(57.7%), 진행이 13예(25.0%)였다. 반응률은 17.3%, 질병통제율은 75.0%였다. 전체 항암 요법 345회 중 용량 감량은 114회에서 시행하였다. 독성이나 부작용으로 인한 사망은 이번 연구에서는 관찰되지 않았다. 가장 흔한 부작용은 빈혈이었다(319회, 92.5%). 독성으로 인해 약제를 변경한 경우는 없었다. 전이의 개수가 적을수록, 혈청 CA 19-9의 수치가 34 U/mL 이하인 경우, 2차항암요법 첫 3주기 시행 이후의 반응이 좋았던 경우에서 총생존기간과 반응 지속기간의 연장을 보였다. 결론: 이번 연구를 통해 진행성 위암에서 2차 항암요법으로 FOLFIRI 요법은 비교적 높은 반응률을 보이며, 부작용이 적어 효과적이면서도 안전한 치료법으로 고려해 볼 수 있겠다. 향후 2차항암치료의 정립을 위해 본 연구가 도움이 될 것으로 생각된다. 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. (Korean J Gastroenterol 2015;66:10-16)

Oxaliplatin, 5-fluorouracil and Leucovorin (FOLFOX-4) Combination Chemotherapy as a Salvage Treatment in Advanced Gastric Cancer

김영생,홍준식,심선진,박세훈,박진희,조은경,이재훈,신동복 대한암학회 2010 Cancer Research and Treatment Vol.42 No.1

Purpose :This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC). Materials and Methods :The AGC patients with an ECOG performance status of 0∼1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m2 on day 1), leucovorin (200 mg/m2 on days 1 and 2) and 5-fluorouracil (400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour infusion on days 1 and 2) every 2 weeks. Results :For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1∼12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progressionfree survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable. Conclusion :Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status.

ERCC1 as a Predictive Marker for FOLFOX Chemotherapy in an Adjuvant Setting

김치영,서상혁,안민성,김광희,배기범,황진원,김지현,김보미,강미선,오민경,홍관희 대한대장항문학회 2015 Annals of Coloproctolgy Vol.31 No.3

Purpose: The purpose of this study was to identify the excision repair cross-complementation group 1 (ERCC1) as a predictive marker for FOLFOX adjuvant chemotherapy in stages II and III colon cancer patients. Methods: A total of 166 high risk stages II and III colon cancer patients were retrospectively enrolled in this study, and data were collected prospectively. They underwent a curative resection followed by FOLFOX4 adjuvant chemotherapy. We analyzed ERCC1 expression in the primary colon tumor by using immunohistochemical staining. The oncological outcomes included the 5-year disease-free survival (DFS) rate. The DFS was analyzed by using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used for the prognostic analysis. Results: ERCC1-positive expression was statistically significant in the older patients (P = 0.032). In the multivariate analysis, the prognostic factors for DFS were female sex (P = 0.016), N stage (P = 0.009), and postoperative carcinoembryonic antigen level (P = 0.001), but ERCC1 expression was not a statistically significant prognostic factor for DFS in the univariate analysis (P = 0.397). The 5-year DFS rate was not significantly associated with the ERCC1 expression in all patients (P = 0.396) or with stage III disease (P = 0.582). Conclusion: We found that ERCC1 expression was not significantly correlated with the 5-year DFS as reflected by the oncologic outcomes in patients with high-risk stages II and III colon cancer treated with FOLFOX adjuvant chemotherapy.