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Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients with Advanced Gastric Cancer
Sung-Hwan Suh, Hyuk-Chan Kwon, Ji-Hoon Jo, Young-Rak Cho, Bong-Gun Seo, Dong-Mee Lee, Sung-Hyun Kim, Jae-Seok Kim, Hyo-Jin Kim
Cancer Res Treat. 2005;37(5):279-283.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.279
AbstractAbstract PDFPubReaderePub
Purpose

To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients.

Materials and Methods

Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on the first day plus LV 20 mg/m2 over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m2 followed by a 22-hour continuous infusion of 600 mg/m2 on days 1~2. The treatment was repeated at 2 week intervals.

Results

The median age of the patients was 50 years (range: 31~74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5~32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6~4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9~9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths.

Conclusion

The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.

Citations

Citations to this article as recorded by  
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    Gyeongyun Go, Chang-Seuk Lee, Yeo Min Yoon, Ji Ho Lim, Tae Hyun Kim, Sang Hun Lee
    International Journal of Molecular Sciences.2021; 22(4): 1976.     CrossRef
  • A Phase I Study of Pevonedistat Plus Capecitabine Plus Oxaliplatin in Patients With Advanced Gastric Cancer Refractory to Platinum (NCCH-1811)
    Hirokazu Shoji, Daisuke Takahari, Hiroki Hara, Kengo Nagashima, Jun Adachi, Narikazu Boku
    Future Science OA.2021;[Epub]     CrossRef
  • Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil in advanced gastric cancer refractory or intolerant to fluoropyrimidines, platinum, taxanes, and irinotecan
    Chihiro Kondoh, Shigenori Kadowaki, Azusa Komori, Yukiya Narita, Hiroya Taniguchi, Takashi Ura, Masashi Ando, Kei Muro
    Gastric Cancer.2018; 21(6): 1050.     CrossRef
  • Pemetrexed for previously treated patients with metastatic gastric cancer: a prospective phase II study
    D S Zhang, Y Jin, H Y Luo, Z Q Wang, M Z Qiu, F H Wang, Y H Li, R H Xu
    British Journal of Cancer.2015; 112(2): 266.     CrossRef
  • Third-line docetaxel chemotherapy for recurrent and metastatic gastric cancer
    Ji Hyun Lee, Sung-Hyun Kim, Sung Yong Oh, Suee Lee, Hojin Lee, Hye Jung Lee, Hyo-Jin Kim
    The Korean Journal of Internal Medicine.2013; 28(3): 314.     CrossRef
  • A Retrospective Study of the Safety and Efficacy of a First-Line Treatment with Modified FOLFOX-4 in Unresectable Advanced or Recurrent Gastric Cancer Patients
    Yung-Sung Yeh, Hsiang-Lin Tsai, Cheng-Jen Ma, Deng-Chyang Wu, Chien-Yu Lu, I-Chen Wu, Ming-Feng Hou, Jaw-Yuan Wang
    Chemotherapy.2012; 58(5): 411.     CrossRef
  • Modified FOLFOX-6 Therapy for Heavily Pretreated Advanced Gastric Cancer Refractory to Fluorouracil, Irinotecan, Cisplatin and Taxanes: A Retrospective Study
    K. Tsuji, H. Yasui, Y. Onozawa, N. Boku, H. Doyama, A. Fukutomi, K. Yamazaki, N. Machida, A. Todaka, H. Taniguchi, T. Tsushima, T. Yokota
    Japanese Journal of Clinical Oncology.2012; 42(8): 686.     CrossRef
  • PEG‐liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase‐8
    Chuang Yang, Hai‐Zhong Liu, Zhong‐Xue Fu
    Cell Biology International.2012; 36(3): 289.     CrossRef
  • Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group
    J G Kim, S K Sohn, Y S Chae, H S Song, K-Y Kwon, Y R Do, M K Kim, K H Lee, M S Hyun, H M Ryoo, S H Bae, K U Park, W S Lee, J H Baek, H Y Chung, W Yu
    British Journal of Cancer.2008; 98(3): 542.     CrossRef
  • A Phase II Study of Paclitaxel and Cisplatin as Salvage Therapy for Patients with Advanced or Metastatic Gastric Cancer
    Bong-Gun Seo, Sung Yong Oh, Dong Mee Lee, Hyun Seung Yoo, Suee Lee, Seong-Geun Kim, Sung-Hyun Kim, Hyuk-Chan Kwon, Hyo-Jin Kim
    Cancer Research and Treatment.2007; 39(1): 6.     CrossRef
  • Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
    H.-C. Kwon, M.S. Roh, S.Y. Oh, S.-H. Kim, M.C. Kim, J.-S. Kim, H.-J. Kim
    Annals of Oncology.2007; 18(3): 504.     CrossRef
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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma
Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee
J Korean Cancer Assoc. 1999;31(1):134-143.
AbstractAbstract PDF
PURPOSE
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy.
MATERIALS AND METHODS
Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%.
RESULTS
Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care.
CONCLUSION
Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.
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Protracted Venous Infusion of 5-Fluorouracil as a Chemotherapy in Colorectal Cancer
Hyun Sik Jeong, Won Seog Kim, Sook In Jung, Jong Tae Lee, Ki Hyun Kim, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Ken Chil Park, Poong Lyul Rhee, Hae Jun Kim, Ho Kyun Chun, Chan Hyung Park
J Korean Cancer Assoc. 1999;31(1):120-125.
AbstractAbstract PDF
PURPOSE
The administration of 5-fluorouracil (5-FU) by protracted intravenous infusion is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancers. This study was performed to evaluate the response rate and toxicities of protracted infusion of 5-FU in patients with advanced or recurrent colorectal cancers who had been treated with 5-FU by bolus or shortterm continuous administration.
MATERIALS AND METHODS
Between March 1995 and June 1997, twenty-eight patients with advanced colorectal cancer previously exposed to 5-FU based chemotherapy were enrolled in this triaL Patients received 5-FU (250 mg/m(2)/day days 1-28) or 5-FU plus leucovorin (5-FU; 200 mg/m/day days 1-28, leucovorin; 20 mg/m IV days 1, 8, 15, 21) by ambulatory infusion pump. Treatment course was repeated every 42 days until disease progression.
RESULT
Twenty-eight patients entered. All 28 patients were assessable for response and toxicity. Five (19%) patients achieved a partial response, with the median response duration of 15 weeks (range; 7-22 weeks), and median survival time of entire patients was 54 weeks (range 7-151+ weeks). Gastrointestinal toxicity, specifically stomatitis was a major toxicity (grade 2, 12%; grade 3, 4%), but hand-foot syndrome was less frequent (5%) compared with other trials with protracted infusion of 5-FU reported in the literature. Hematologic toxicity was generally of low grade.
CONCLUSION
Prolonged intravenous infusion of 5-FU can produce a response rate of 19% with low toxicity among patients refractory to bolus or short-term infusion of S-FU.
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