Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

V Catalano, F Graziano, D Santini, S D'Emidio, A M Baldelli, D Rossi, B Vincenzi, P Giordani, P Alessandroni, E Testa, G Tonini, G Catalano, V Catalano, F Graziano, D Santini, S D'Emidio, A M Baldelli, D Rossi, B Vincenzi, P Giordani, P Alessandroni, E Testa, G Tonini, G Catalano

Abstract

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin </=11.5 g l(-1) (HR, 1.48; 95% CI, 1.06-2.05; P=0.019), CEA level >50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy </=6 months (HR, 1.97; 95% CI, 1.39-2.80; P<0.0001). A prognostic index was constructed dividing patients into low- (no risk factor), intermediate- (one to two risk factors), or high- (three to five risk factors) risk groups, and median survival times for each group were 12.7 months, 7.1 months, and 3.3 months, respectively (P<0.001). In the absence of data deriving from randomised trials, this analysis suggests that some easily available clinical factors may help to select patients with advanced gastric cancer who could derive more benefit from second-line chemotherapy.

Figures

Figure 1
Figure 1
Overall survival curve for the whole group (n=175).
Figure 2
Figure 2
Survival curves according to the risk groups. Marks on survival curves denote censored observations.

References

    1. Ajani JA (2005) Evolving chemotherapy for advanced gastric cancer. Oncologist 10(Suppl 3): 49–58
    1. Al-Batran S, Hartmann J, Probst S, Hofheinz R, Stoehlmacher H, Schmalenberg H, Hollerbach S, Schuch G, Homann N, Jäger E (2006) A randomized phase III trial in patients with advanced adenocarcinoma of the stomach receiving first-line chemotherapy with fluorouracil, leucovorin and oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP). J Clin Oncol 24(Suppl 18): LBA4016a
    1. Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F, Van Cutsem E (2005) Gastric cancer. Crit Rev Oncol Hematol 54: 209–241
    1. Chau I, Norman AR, Ross PJ, Waters JS, Oates J, Cunningham D (2004a) Multivariate prognostic factor analysis and second-line treatment in locally advanced and metastatic oesophago-gastric cancer – pooled analysis of 1080 patients from three multicentre randomised controlled trials using individual patient data. ASCO Gastrointestinal Cancers Symposium; abstract 5
    1. Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ (2004b) Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer—pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol 22: 2395–2403
    1. Colombo N, Van Gorp T, Parma G, Amant F, Gatta G, Sessa C, Vergote I (2006) Ovarian cancer. Crit Rev Oncol Hematol 60: 159–179
    1. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 58: 36–46
    1. Dank M, Zaluski J, Barone C, Valvere V, Peschel C, Wenczl M, Goker E, Risse M, Awad L, Bugat R (2005) Randomized phase 3 trial of irinotecan (CPT-11)+5FU/folinic acid (FA) vs CDDP+5FU in 1st-line advanced gastric cancer patients. J Clin Oncol 23(Suppl 16): 4003a.
    1. Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjödén PO, Haglund U, Svensson C, Enander LK, Linné T, Sellström H, Heuman R (1997) Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8: 163–168
    1. Goldberg RM, Rothenberg ML, Van Cutsem E, Benson III AB, Blanke CD, Diasio RB, Grothey A, Lenz HJ, Meropol NJ, Ramanathan RK, Becerra CH, Wickham R, Armstrong D, Viele C (2007) The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 12: 38–50
    1. Holyoke ED, Chu TM, Murphy GP (1975) CEA as a monitor of gastrointestinal malignancy. Cancer 35: 830–836
    1. Hostetter RJ, Augustus LB, Mankarious R, Chi KF, Fan D, Toth C, Thomas P, Jessup JM (1990) Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Natl Cancer Inst 82: 380–385
    1. Ikeda Y, Oomori H, Koyanagi N, Mori M, Kamakura T, Minagawa S, Tateishi H, Sugimachi K (1995) Prognostic value of combination assays for CEA and CA 19-9 in gastric cancer. Oncology 52: 483–486
    1. Kang Y, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Salas MP, Suarez T, Santamaria J (2006) Randomized phase III trial of capecitabine/cisplatin (XP) vs. continuous infusion of 5-FU/cisplatin (FP) as first-line therapy in patients (pts) with advanced gastric cancer (AGC): efficacy and safety results. J Clin Oncol 24(Suppl 18): LBA4018a
    1. Kaplan EL, Meier P (1958) Non parametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481
    1. Kochi M, Fujii M, Kanamori N, Kaiga T, Kawakami T, Aizaki K, Kasahara M, Mochizuki F, Kasakura Y, Yamagata M (2000) Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with gastric cancer. Gastric Cancer 3: 177–186
    1. Korenaga D, Funahashi S, Yano K, Maekawa S, Ikeda T, Sugimachi K (1995) Relationship between peritoneal collagen type IV concentrations and the presence of disseminated metastases in gastric cancer. Arch Surg 130: 769–773
    1. Lee J, Lim T, Uhm JE, Park KW, Park SH, Lee SC, Park JO, Park YS, Lim HY, Sohn TS, Noh JH, Heo JS, Park CK, Kim S, Kang WK (2007) Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma. Ann Oncol 18: 886–891
    1. Louvet C, Carrat F, Mal F, Mabro M, Beerblock K, Vaillant JC, Cady J, André T, Gamelin E, de Gramont A (2003) Prognostic factor analysis in advanced gastric cancer patients treated with hydroxyurea, leucovorin, 5-fluorouracil, and cisplatin (HLFP regimen). Cancer Invest 21: 14–20
    1. Macdonald JS (2006) Gastric cancer—new therapeutic options. N Engl J Med 355: 76–77
    1. Mitry E, Douillard JY, Van Cutsem E, Cunningham D, Magherini E, Mery-Mignard D, Awad L, Rougier P (2004) Predictive factors of survival in patients with advanced colorectal cancer: an individual data analysis of 602 patients included in irinotecan phase III trials. Ann Oncol 15: 1013–1017
    1. Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M (1993) Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72: 37–41
    1. Park SH, Lee J, Lee SH, Park JO, Kim K, Kim WS, Jung CW, Park YS, Kang WK, Park K, Kim S, Bang SM, Cho EK, Shin DB, Lee JH (2006) Anemia is the strongest prognostic factor for outcomes of 5-fluorouracil-based first-line chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol 57: 91–96
    1. Parkin DM, Pisani P, Ferlay J (1999) Global Cancer Statistics. CA Cancer J Clin 49: 33–64
    1. Peto R, Peto J (1972) Asymptotically efficient invariant procedures. JR Stat Soc A 135: 185–206
    1. Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M (1995) 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 71: 587–591
    1. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, Gilly FN (2000) Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE-1 multicentric prospective study. Cancer 88: 358–363
    1. Sastre J, Garcia-Saenz JA, Diaz-Rubio E (2006) Chemotherapy for gastric cancer. World J Gastroenterol 12: 204–213
    1. Schöffski P (2002) New drugs for treatment of gastric cancer. Ann Oncol 13(Suppl 4): 13–22
    1. Stahl M, Müller C, Köster W, Wilke H (2005) Second-line chemotherapy of advanced disseminated gastric cancer after cisplatin, infusional 5-fluorouracil, folinic acid (PLF): benefit dependent on progression-free interval after first-line therapy. Onkologie 28: 499–502
    1. Tachibana M, Takemoto Y, Nakashima Y, Kinugasa S, Kotoh T, Dhar DK, Kohno H, Nagasue N (1998) Serum carcinoembryonic antigen as a prognostic factor in resectable gastric cancer. J Am Coll Surg 187: 64–68
    1. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92: 205–216
    1. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA, V325 Study Group (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 study group. J Clin Oncol 24: 4991–4997
    1. Vansteenkiste J (2007) Improving patient management in metastatic non-small cell lung cancer. Lung Cancer 57(Suppl 2): 12–17
    1. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE (2006) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24: 2903–2909
    1. Wilson D, Hiller L, Geh JI (2005) Review of second-line chemotherapy for advanced gastric adenocarcinoma. Clin Oncol 17: 81–90
    1. Yoshida M, Ohtsu A, Boku N, Miyata Y, Shirao K, Shimada Y, Hyodo I, Koizumi W, Kurihara M, Yoshida S, Yamamoto S (2004) Long-term survival and prognostic factors in patients with metastatic gastric cancers treated with chemotherapy in the Japan Clinical Oncology Group (JCOG) study. Jpn J Clin Oncol 34: 654–659

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