J Korean Med Sci.  2004 Jun;19(3):369-373. 10.3346/jkms.2004.19.3.369.

Combination Chemotherapy with 5-Fluorouracil and Heptaplatin as First-line Treatment in Patients with Advanced Gastric Cancer

• Min YJ
• Bang SJ
• Shin JW
• Kim DH
• Park JH
• Kim GY
• Ko BK
• Choi DH
• Cho HR

• KMID: 1786814
• DOI: http://doi.org/10.3346/jkms.2004.19.3.369

Abstract

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

Keyword

Drug Therapy; Fluorouracil; Stomach Neoplasms; Heptaplatin; Platinum Compounds

MeSH Terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Disease-Free Survival
Female
Fluorouracil/*administration & dosage
Follow-Up Studies
Human
Male
Malonates/*administration & dosage
Middle Aged
Organoplatinum Compounds/*administration & dosage
Stomach Neoplasms/*drug therapy
Time Factors
Treatment Outcome

Figure

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  Fig. 1 (A) Duration of response, (B) Progression free survival.

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  Fig. 2 (A) Overall survival, (B) Effect of performance status on overall survival.

Reference

1. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics 2002. CA Cancer J Clin. 2002. 52:23–47.

2. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics 2001. CA Cancer J Clin. 2001. 51:15–36.

3. Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer. 1995. 71:587–591.

4. Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993. 72:37–41.

5. Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom H, Heuman R. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997. 8:163–168.

6. Alberts SR, Cervantes A, van de Velde CJ. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003. 14:Suppl 2. ii31–ii36.

7. Kim DK, Kim G, Gam J, Cho YB, Kim HT, Tai JH, Kim KH, Hong WS, Park JG. Synthesis and antitumor activity of a series of [2-substituted-4,5-bis(aminomethyl)-1,3-dioxolane]platinum(II) complexes. J Med Chem. 1994. 37:1471–1485.

8. Kim DK, Kim HT, Cho YB, Tai JH, Ahn JS, Kim TS, Kim KH, Hong WS. Antitumor activity of cis-malonato[(4R, 5R)-4,5 bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II), a new platinum analogue, as an anticancer agent. Cancer Chemother Pharmacol. 1995. 35:441–445.

9. Kim HT, Kim DK, Cho YB, Kim TS, Jung I, Kim KH, Heo DS, Bang YJ, Shin SG, Kim NK. Influence of exposure and infusion times on the cytotoxicity and pharmacokinetics of cis-malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II). Cancer Chemother Pharmacol. 1998. 41:109–116.

10. Kim NK, Im SA, Kim DW, Lee MH, Jung CW, Cho EK, Lee JT, Ahn JS, Heo DS, Bang YJ. Phase II clinical trial of SKI-2053R, a new platinum analog, in the treatment of patients with advanced gastric adenocarcinoma. Cancer. 1999. 86:1109–1115.

11. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. J Nat Cancer Inst. 2000. 92:205–216.

12. Lacave AJ, Barón FJ, Antón LM, Estrada E, De Sande LM, Palacio I, Esteban E, Gracia JM, Buesa JM, Fernández OA, Barón MG. Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol. 1991. 2:751–754.

13. Rougier P, Ducreux M, Mahjoubi M, Pignon JP, Bellefqih S, Oliveira J, Bognel C, Lasser P, Ychou M, Elias D, Cvitkovic E, Armand JP, Droz JP. Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas: a phase II trial with prognostic factor analysis. Eur J Cancer. 1994. 30:1263–1269.

14. Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997. 15:261–267.

15. Preusser P, Wilke H, Achterrath W, Fink U, Lenaz L, Heinicke A, Meyer J, Meyer HJ, Buente H. Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer. J Clin Oncol. 1989. 7:1310–1317.

16. Cascinu S, Labianca R, Alessandroni P, Marcellini M, Silva RR, Pancera G, Testa E, Martignoni G, Barni S, Frontini L, Zaniboni A, Luporini G, Cellerino R, Catalano G. Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian group for the study of digestive tract cancer. J Clin Oncol. 1997. 15:3313–3319.

17. Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994. 5:609–616.

18. Ahn JH, Kang YK, Kim TW, Bahng H, Chang HM, Kang WC, Kim WK, Lee JS, Park JS. Nephrotoxicity of heptaplatin: a randomized comparison with cisplatin in advanced gastric cancer. Cancer Chemother Pharmacol. 2002. 50:104–110.