Reduced Dose Intensity FOLFOX-4 as First Line Palliative Chemotherapy in Elderly Patients with Advanced Colorectal Cancer

Purpose To determine the tolerability of capecitabine in elderly patients with advanced colorectal cancer (CRC). Patients and Methods Fifty-one patients with advanced CRC who were ≥ 70 years and considered ineligible for combination chemotherapy received oral capecitabine 1,250 mg/m2 twice daily on days 1 to 14 every 3 weeks. Patients with a creatinine clearance of 30 to 50 mL/min received a dose of 950 mg/m2 twice daily. Results A total of 248 cycles of capecitabine were administered (median, five cycles; range, one to eight cycles). The overall response rate was 24% (95% CI, 15% to 41%), including two complete responses (CR; 4%) and 10 partial responses (PR; 20%). Disease control (CR + PR + stable disease) was achieved in 67% of patients. The median times to disease progression and overall survival were 7 months (95% CI, 6.4 to 9.5 months) and 11 months (95% CI, 8.6 to 13.3 months), respectively. Of the 35 patients evaluated for clinical benefit response, 14 (40%; 95% CI, 24% to 58%) showed clinical benefit. Capecitabine was well tolerated. Treatment-related grade 3 and 4 adverse events were observed in only six patients (12%), and the most common events were diarrhea, hand-foot syndrome, and thrombocytopenia. One patient (2%) had an episode of angina, but no treatment-related deaths were reported. Conclusion Our findings suggest that capecitabine is effective and well tolerated in elderly patients with advanced CRC who are considered ineligible for combination chemotherapy.

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Pharmacogenetic Profiling in Patients With Advanced Colorectal Cancer Treated With First-Line FOLFOX-4 Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2006.08.1844 ◽

2007 ◽

Vol 25 (10) ◽

pp. 1247-1254 ◽

Cited By ~ 206

Author(s):

Annamaria Ruzzo ◽

Francesco Graziano ◽

Fotios Loupakis ◽

Eliana Rulli ◽

Emanuele Canestrari ◽

...

Keyword(s):

Colorectal Cancer ◽

Methylenetetrahydrofolate Reductase ◽

Advanced Colorectal Cancer ◽

Palliative Chemotherapy ◽

Excision Repair ◽

Central Italy ◽

First Line ◽

Innovative Strategy ◽

X Ray ◽

Group 1

Purpose The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy. Materials and Methods Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion. Peripheral blood samples were used for genotyping 12 polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase, xeroderma pigmentosum group D (XPD), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing group 1, x-ray cross complementing protein 3, glutathione S-transferases (GSTs) genes. The primary end point of the study was to investigate the association between genotypes and progression-free survival (PFS). Results In 166 patients, ERCC1-118 T/T, XPD-751 A/C, and XPD-751 C/C genotypes were independently associated with adverse PFS. The presence of two risk genotypes (ERCC1-118 T/T combined with either XPD-751 A/C or XPD-751 C/C) occurred in 50 patients (31%). This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84% and 95% CI of 1.47 to 5.45 (P = .002). Neurotoxicity was significantly associated with GSTP1-105 A/G. Carriers of the GSTP1-105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1-105 A/G and GSTP1-105 A/A genotypes. Conclusion A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.

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4004 Cetuximab plus capecitabine as first-line treatment for elderly patients (pts) with advanced colorectal cancer (mCRC). Final analysis of activity and survival according to KRAS status – the TTD-06–01 Spanish Cooperative Group trial

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)70738-4 ◽

2009 ◽

Vol 7 (2) ◽

pp. 216 ◽

Cited By ~ 2

Author(s):

F. Rivera ◽

C. Gravalos ◽

B. Massutí ◽

J. Puente ◽

E. Marcuello ◽

...

Keyword(s):

Colorectal Cancer ◽

Elderly Patients ◽

Advanced Colorectal Cancer ◽

Final Analysis ◽

Cooperative Group ◽

Line Treatment ◽

First Line ◽

Kras Status ◽

Group Trial ◽

First Line Treatment

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Geriatric factors to predict toxicity and dose-intensity reduction in FFCD 2001-02 phase III study comparing a first-line chemotherapy of LV5FU2 or FOLFIRI in treatment of metastatic colorectal cancer (mCRC) in elderly patients.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.9111 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 9111-9111 ◽

Cited By ~ 2

Author(s):

T. Aparicio ◽

J. Jouve ◽

L. Teillet ◽

D. Gargot ◽

V. Le Brun Ly ◽

...

Keyword(s):

Colorectal Cancer ◽

Elderly Patients ◽

Metastatic Colorectal Cancer ◽

Dose Intensity ◽

Phase Iii ◽

First Line ◽

Phase Iii Study ◽

Line Chemotherapy

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Bolus Fluorouracil and Leucovorin With Oxaliplatin as First-Line Treatment in Metastatic Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2002.08.144 ◽

2002 ◽

Vol 20 (10) ◽

pp. 2545-2550 ◽

Cited By ~ 30

Author(s):

Alberto Ravaioli ◽

Maurizio Marangolo ◽

Enzo Pasquini ◽

Andrea Rossi ◽

Dino Amadori ◽

...

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

Performance Status ◽

Initial Dosage ◽

Dose Intensity ◽

Progression Free Survival ◽

Bolus Administration ◽

First Line ◽

First Line Therapy ◽

Duration Of Response

PURPOSE: A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer. PATIENTS AND METHODS: Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m2 on the first day of each course and 5-FU and LV 350 mg/m2 and 20 mg/m2, respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses. RESULTS: Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m2. Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION: Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m2 dosage offered improved dose-intensity compared with the initial dosage.

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