Capecitabine plus oxaliplatin for the first‐line treatment of elderly patients with metastatic colorectal carcinoma

Abstract

BACKGROUNDIn patients with metastatic colorectal carcinoma (MCC), capecitabine has demonstrated a superior response rate (RR), equivalent disease progression‐free (PFS) and overall survival (OS), and an improved overall tolerability profile compared with bolus 5‐fluorouracil/leucovorin (5‐FU/LV). The FOLFOX4 regimen, combining oxaliplatin with LV and bolus plus infusional 5‐FU (LV5FU2), has been shown to improve RR and PFS versus LV5FU2, and it was more effective and less toxic than irinotecan plus bolus 5‐FU/LV. Capecitabine (an oral fluoropyrimidine) may be an effective, well tolerated, and more convenient alternative to 5‐FU/LV in combination with oxaliplatin, especially in older patients.METHODSElderly (≥ 70 years) patients with MCC were treated with a 3‐weekly regimen of oxaliplatin at an initial dose of 85 mg/m2 intravenously on Day 1 plus capecitabine 1000 mg/m2 orally twice daily from Days 2 to 15 (XELOX regimen). In the absence of Grade ≥ 2 hematologic toxicity, oxaliplatin was increased to 100 mg/m2 in the second cycle, and in the absence of Grade ≥ 2 nonhematologic adverse events during Cycle 2, capecitabine was increased to 1250 mg/m2 twice daily in the third and subsequent cycles. After the first 35 patients (first series), the treatment protocol was amended so that only an oxaliplatin increase to 110 mg/m2 and 130 mg/m2 during Cycles 2 and 3, respectively, was planned in the remaining 41 patients (second series).RESULTSSeventy‐six patients with a median age of 75 years (range, 70–82 years) entered the current study. In the first series, the oxaliplatin dose was increased in 18 (51%) patients, and the capecitabine dose was increased in 4 (11%) patients. In the second series, the oxaliplatin dose was increased to 110 mg/m2 in 26 (63%) patients, and to 130 mg/m2 in 19 (46%) patients. In all, 2 complete and 29 partial responses were observed, for an overall RR of 41% (95% confidence interval [CI], 30–53%). The median PFS was 8.5 months (95% CI, 6.7–10.3 months), and the median OS was 14.4 months (95% CI, 11.9–16.9 months). In a multivariate analysis, the presence of disease symptoms affected both PFS and OS, whereas OS also was independently affected by male gender and disease spread. Age had no independent effect on PFS or OS. Five percent of patients developed Grade ≥ 3 hematologic toxicity during treatment, Grade 3 peripheral neuropathy occurred in 8% of patients, and severe hand‐foot syndrome in 13% of patients.CONCLUSIONSFit elderly patients with MCC showed a good RR to XELOX with only mild toxicity observed in most patients. XELOX, should, therefore be considered as an important therapeutic option for elderly patients with MCC. Cancer 2005. © 2005 American Cancer Society.

XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer

“…However, given that the development of this toxicity depends on the total accumulated dose of oxaliplatin received during treatment, the low toxicity in our series can probably be attributed to the reduced number of treatment cycles received by our patients compared to the series of Cassidy et al (2004) (median 4.5 vs 8 cycles, respectively). On the other hand, the proportion of the elderly in our study that developed grade 3/4 adverse events was similar to the 29% reported in another study performed exclusively in the elderly and which also used a capecitabine/oxaliplatin regimen, in which the dose of subsequent cycles was increased as a function of tolerability by the patient (Comella et al, 2005).…”

“…In contrast, median overall survival in our series was 13.2 months, which is somewhat less than the 17 -20 months reached in these other studies (Borner et al, 2002a;Zeuli et al, 2003;Cassidy et al, 2004). However, median overall survival was similar to that obtained in studies performed exclusively in the elderly with MCRC who received combinations of 5-FU/LV plus oxaliplatin or irinotecan (Aparicio et al, 2003), or capecitabine plus oxaliplatin (Comella et al, 2005). It has been noted that the survival of patients with MCRC increases when they receive three active cytostatic agents (5-FU/LV, oxaliplatin, and irinotecan) during their disease course (Grothey et al, 2004;Tournigand et al, 2004).…”

Capecitabine plus oxaliplatin compared with 5-fluorouracil plus oxaliplatin in metastatic colorectal cancer: Meta-analysis of randomized controlled trials

“…Recently, more attention has been paid to combination chemotherapy of CRC with the regimen of capecitabine and oxaliplatin for safe, reliable and convenient medication. In certain randomized studies it was concluded that XELOX is non-inferior in terms of efficacy to the FOLFOX regimen in the first-line treatment of MCRC (5)(6)(7)9,11 Regarding adverse reactions during treatment, 5% of patients had Grade ≥3 hematologic toxicity, 8% of patients had Grade 3 peripheral neuropathy and 13% of patients had severe hand-foot syndrome (19). Similar results were obtained in another phase II trial that included a total of 50 patients aged ﹥70 years with MCRC, using the XELOX regimen as first-line therapy.…”

An elderly patient with marginally unresectable rectal cancer obtained pathological complete response by the treatment with mFOLFOX6

“…Since general surgeons often perform chemotherapy in Japan, they are quite accustomed to the use of oxaliplatin. Therefore Japanese oncologists including gastrointestinal and general surgeons can often perform chemotherapy for elderly patients with oxaliplatin based regimens 1) .…”