Abstract
OBJECTIVE: In Western populations, long-term survival rates after curative resection of gastric cancer remain extremely poor. The lack of effective adjuvant therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we have conducted three separate phase II trials using neoadjuvant chemotherapy to treat patients with potentially resectable gastric cancer. The present study was conducted to evaluate whether response to neoadjuvant chemotherapy is predictive of survival in patients with resectable gastric cancer. METHODS: Eighty-three patients with pathologically confirmed gastric adenocarcinoma were treated with neoadjuvant chemotherapy before planned surgical resection. Response was assessed by upper gastrointestinal series, endoscopy, computed tomography scan, and pathologic examination. RESULTS: For the three phase II trials, clinical response rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic response. Sixty-one patients (73%) underwent a curative resection. Median follow-up was 26 months. Univariate analysis revealed T stage, number of positive nodes, and response to chemotherapy to be significant predictors of overall survival. However, on multivariate analysis, response to chemotherapy was found to be the only independent prognostic factor. CONCLUSIONS: Response to neoadjuvant chemotherapy is the single most important predictor of overall survival after neoadjuvant chemotherapy for gastric cancer. These findings support further evaluation of neoadjuvant approaches in the treatment of this disease.
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- Ajani J. A., Mansfield P. F., Ota D. M. Potentially resectable gastric carcinoma: current approaches to staging and preoperative therapy. World J Surg. 1995 Mar-Apr;19(2):216–220. doi: 10.1007/BF00308629. [DOI] [PubMed] [Google Scholar]
- Ajani J. A., Mayer R. J., Ota D. M., Steele G. D., Evans D., Roh M., Sugarbaker D. J., Dumas P., Gray C., Vena D. A. Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma. J Natl Cancer Inst. 1993 Nov 17;85(22):1839–1844. doi: 10.1093/jnci/85.22.1839. [DOI] [PubMed] [Google Scholar]
- Ajani J. A., Ota D. M., Jessup J. M., Ames F. C., McBride C., Boddie A., Levin B., Jackson D. E., Roh M., Hohn D. Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy. Cancer. 1991 Oct 1;68(7):1501–1506. doi: 10.1002/1097-0142(19911001)68:7<1501::aid-cncr2820680706>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
- Alexander H. R., Grem J. L., Pass H. I., Hamilton M., McAtee N., Fraker D. L., Allegra C. J. Neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma. Oncology (Williston Park) 1993 May;7(5):37-42; discussion 42-4, 49-50, 53. [PubMed] [Google Scholar]
- Anderson J. R., Cain K. C., Gelber R. D. Analysis of survival by tumor response. J Clin Oncol. 1983 Nov;1(11):710–719. doi: 10.1200/JCO.1983.1.11.710. [DOI] [PubMed] [Google Scholar]
- Bemelman W. A., van Delden O. M., van Lanschot J. J., de Wit L. T., Smits N. J., Fockens P., Gouma D. J., Obertop H. Laparoscopy and laparoscopic ultrasonography in staging of carcinoma of the esophagus and gastric cardia. J Am Coll Surg. 1995 Nov;181(5):421–425. [PubMed] [Google Scholar]
- Burke E. C., Karpeh M. S., Conlon K. C., Brennan M. F. Laparoscopy in the management of gastric adenocarcinoma. Ann Surg. 1997 Mar;225(3):262–267. doi: 10.1097/00000658-199703000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caletti G., Ferrari A., Brocchi E., Barbara L. Accuracy of endoscopic ultrasonography in the diagnosis and staging of gastric cancer and lymphoma. Surgery. 1993 Jan;113(1):14–27. [PubMed] [Google Scholar]
- Clark J. L., Barcewicz P., Nava H. R., Goodwin P. S., Douglass H. O., Jr Adjuvant 5-FU and MeCCNU improves survival following curative gastrectomy for adenocarcinoma. Am Surg. 1990 Jul;56(7):423–427. [PubMed] [Google Scholar]
- Engstrom P. F., Lavin P. T., Douglass H. O., Jr, Brunner K. W. Postoperative adjuvant 5-fluorouracil plus methyl-CCNU therapy for gastric cancer patients. Eastern Cooperative Oncology Group study (EST 3275). Cancer. 1985 May 1;55(9):1868–1873. doi: 10.1002/1097-0142(19850501)55:9<1868::aid-cncr2820550904>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
- Fastenberg N. A., Martin R. G., Buzdar A. U., Hortobagyi G. N., Montague E. D., Blumenschein G. R., Jessup J. M. Management of inflammatory carcinoma of the breast. A combined modality approach. Am J Clin Oncol. 1985 Apr;8(2):134–141. doi: 10.1097/00000421-198504000-00005. [DOI] [PubMed] [Google Scholar]
- Feldman L. D., Hortobagyi G. N., Buzdar A. U., Ames F. C., Blumenschein G. R. Pathological assessment of response to induction chemotherapy in breast cancer. Cancer Res. 1986 May;46(5):2578–2581. [PubMed] [Google Scholar]
- Fink U., Stein H. J., Schuhmacher C., Wilke H. J. Neoadjuvant chemotherapy for gastric cancer: update. World J Surg. 1995 Jul-Aug;19(4):509–516. doi: 10.1007/BF00294711. [DOI] [PubMed] [Google Scholar]
- Gez E., Sulkes A., Yablonsky-Peretz T., Weshler Z. Combined 5-fluorouracil (5-FU) and radiation therapy following resection of locally advanced gastric carcinoma. J Surg Oncol. 1986 Feb;31(2):139–142. doi: 10.1002/jso.2930310213. [DOI] [PubMed] [Google Scholar]
- Gunderson L. L., Hoskins R. B., Cohen A. C., Kaufman S., Wood W. C., Carey R. W. Combined modality treatment of gastric cancer. Int J Radiat Oncol Biol Phys. 1983 Jul;9(7):965–975. doi: 10.1016/0360-3016(83)90383-8. [DOI] [PubMed] [Google Scholar]
- Gunderson L. L., Sosin H. Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. 1982 Jan;8(1):1–11. doi: 10.1016/0360-3016(82)90377-7. [DOI] [PubMed] [Google Scholar]
- Hermans J., Bonenkamp J. J., Boon M. C., Bunt A. M., Ohyama S., Sasako M., Van de Velde C. J. Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials. J Clin Oncol. 1993 Aug;11(8):1441–1447. doi: 10.1200/JCO.1993.11.8.1441. [DOI] [PubMed] [Google Scholar]
- Higgins G. A., Amadeo J. H., Smith D. E., Humphrey E. W., Keehn R. J. Efficacy of prolonged intermittent therapy with combined 5-FU and methyl-CCNU following resection for gastric carcinoma. A Veterans Administration Surgical Oncology, Group report. Cancer. 1983 Sep 15;52(6):1105–1112. doi: 10.1002/1097-0142(19830915)52:6<1105::aid-cncr2820520629>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Joypaul B. V., Hopwood D., Newman E. L., Qureshi S., Grant A., Ogston S. A., Lane D. P., Cuschieri A. The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma. Br J Cancer. 1994 May;69(5):943–946. doi: 10.1038/bjc.1994.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landis S. H., Murray T., Bolden S., Wingo P. A. Cancer statistics, 1998. CA Cancer J Clin. 1998 Jan-Feb;48(1):6–29. doi: 10.3322/canjclin.48.1.6. [DOI] [PubMed] [Google Scholar]
- Landry J., Tepper J. E., Wood W. C., Moulton E. O., Koerner F., Sullinger J. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1357–1362. doi: 10.1016/0360-3016(90)90344-j. [DOI] [PubMed] [Google Scholar]
- Leach S. D., Lowy A. M., Mansfield P. F., Ajani J. A. Adjuvant therapy for resectable gastric adenocarcinoma: preoperative and postoperative chemotherapy trials. J Infus Chemother. 1995 Summer;5(3):104–111. [PubMed] [Google Scholar]
- Leichman L., Silberman H., Leichman C. G., Spears C. P., Ray M., Muggia F. M., Kiyabu M., Radin R., Laine L., Stain S. Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: a University of Southern California pilot program. J Clin Oncol. 1992 Dec;10(12):1933–1942. doi: 10.1200/JCO.1992.10.12.1933. [DOI] [PubMed] [Google Scholar]
- Lenz H. J., Leichman C. G., Danenberg K. D., Danenberg P. V., Groshen S., Cohen H., Laine L., Crookes P., Silberman H., Baranda J. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol. 1996 Jan;14(1):176–182. doi: 10.1200/JCO.1996.14.1.176. [DOI] [PubMed] [Google Scholar]
- Lowy A. M., Mansfield P. F., Leach S. D., Ajani J. Laparoscopic staging for gastric cancer. Surgery. 1996 Jun;119(6):611–614. doi: 10.1016/s0039-6060(96)80184-x. [DOI] [PubMed] [Google Scholar]
- Martin H. M., Filipe M. I., Morris R. W., Lane D. P., Silvestre F. p53 expression and prognosis in gastric carcinoma. Int J Cancer. 1992 Apr 1;50(6):859–862. doi: 10.1002/ijc.2910500604. [DOI] [PubMed] [Google Scholar]
- Moertel C. G., Childs D. S., O'Fallon J. R., Holbrook M. A., Schutt A. J., Reitemeier R. J. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. J Clin Oncol. 1984 Nov;2(11):1249–1254. doi: 10.1200/JCO.1984.2.11.1249. [DOI] [PubMed] [Google Scholar]
- Plukker J. T., Mulder N. H., Sleijfer D. T., Grond J., Verschueren R. C. Chemotherapy and surgery for locally advanced cancer of the cardia and fundus: phase II study with methotrexate and 5-fluorouracil. Br J Surg. 1991 Aug;78(8):955–958. doi: 10.1002/bjs.1800780820. [DOI] [PubMed] [Google Scholar]
- Regine W. F., Mohiuddin M. Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys. 1992;24(5):921–927. doi: 10.1016/0360-3016(92)90476-x. [DOI] [PubMed] [Google Scholar]
- Shiu M. H., Perrotti M., Brennan M. F. Adenocarcinoma of the stomach: a multivariate analysis of clinical, pathologic and treatment factors. Hepatogastroenterology. 1989 Feb;36(1):7–12. [PubMed] [Google Scholar]
- Tio T. L., Schouwink M. H., Cikot R. J., Tytgat G. N. Preoperative TNM classification of gastric carcinoma by endosonography in comparison with the pathological TNM system: a prospective study of 72 cases. Hepatogastroenterology. 1989 Apr;36(2):51–56. [PubMed] [Google Scholar]
- Walsh T. N., Noonan N., Hollywood D., Kelly A., Keeling N., Hennessy T. P. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462–467. doi: 10.1056/NEJM199608153350702. [DOI] [PubMed] [Google Scholar]
- Wanebo H. J., Kennedy B. J., Chmiel J., Steele G., Jr, Winchester D., Osteen R. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993 Nov;218(5):583–592. doi: 10.1097/00000658-199321850-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilke H., Preusser P., Fink U., Gunzer U., Meyer H. J., Meyer J., Siewert J. R., Achterrath W., Lenaz L., Knipp H. Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin. J Clin Oncol. 1989 Sep;7(9):1318–1326. doi: 10.1200/JCO.1989.7.9.1318. [DOI] [PubMed] [Google Scholar]