3737 Background: The improved safety profile of the oral fluoropyrimidine X (Xeloda) versus bolus 5-FU/LV has been demonstrated in over 3000 pts in 3 large randomized trials in 1(st) line metastatic and adjuvant colon cancer (Twelves EJC 2002, Scheithauer Ann Oncol 2003). In addition, the safety advantage over 5-FU/LV in the adjuvant setting was maintained in older pts (≥65 years) and also in terms of less early severe toxicity with X. The median age of pts at diagnosis of colon cancer is increasing in developed countries. Therefore we examined whether there is enough evidence to support the safe use of X in an elderly population, i.e. pts 70 years and older.
METHODS: We performed retrospective analyses on the safety database of the X-ACT adjuvant colon cancer trial, which compared X (993 pts) to 5-FU/LV Mayo Clinic Regimen (974 pts) in Dukes' C colon cancer pts. Adverse events (AEs) in the two arms were analyzed by age: <40, 41-69 and ≥70 years. P-values are not calculated due to the retrospective nature of analysis.
RESULTS: Sufficient patient numbers enable comparisons between X and 5-FU/LV for the 41-69 age group (763 vs 738, not shown) and ≥70 group (186 vs 205, table), whereas there were few pts aged <40 (44 vs 31, not shown). [Figure: see text] Hyperbilirubinemia was minimal in both arms when graded by NCI CTCAE.
CONCLUSIONS: The improved safety profile of X vs 5-FU/LV is not only maintained in pts over 65, but also in the elderly over 70 years of age. It would be of interest to compare this dataset to that of the INT 0089 trial (Mayo Clinic regimen vs Roswell Park weekly bolus regimen). Pending the final results of the X-ACT study, capecitabine could provide a convenient and effective new option for an aging population. Study sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. No significant financial relationships to disclose.
CONCLUSION: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.
TREATMENT: Rx 375 mg/m(2) IV at day 1; concomitant therapy: Rasburicase, steroids only for anaphylaxis, intrathecal (IT) triple drug at days 1, 3 for CNS pts only. Begin of chemotherapy at day 5. Response evaluation: product of 2 perpendicular diameters of 1 - 3 index lesions/% blasts in BM/PB within 24 h prior to Rx and at day 5: responder (RP): at least 1 lesion with at least objective effect (decrease of ≥25%) and no progress (increase of ≥25 %) at other sites. Study plan: Simon 2-stage phase II with α and β = 5%. Response rate (RR) for poor activity was set to 45%, for good activity 65%. 33 pts entered the first stage, final evaluation after 79 pts.
METHOD: Patterns of skeletal (123)I mIBG uptake were assignednumerical scores (Mscore) ranging from 0 (no metastasis) to 72 (diffuse metastases) within 12 body areas as described previously (J Nucl Med 2009;50:1379). 271 anonymised, paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were reviewed, constituting a representative sample of 1602 children treated prospectively within the HR-NBL1/SIOPEN trial. Pre-and post-treatment Mscores were compared with bone marrow cytology (BM) and 3 year event free survival (EFS).
THERAPY: The indirect cost savings in terms of the value of patient time are substantial. Other potential cost factors, including hospital use, ambulatory encounters, and other medications, did not differ significantly between the regimens. If this trial meets its primary endpoint of equivalence in disease-free survival, X is likely to be cost-effective from a societal perspective compared with the Mayo Clinic regimen in the adjuvant treatment of Dukes' C colon cancer. [Table: see text].
EXCLUSIONS: brain metastases; prior chemotherapy. Pre-randomization strata: Liver metastases (Y/N); other visceral metastases or elevated serum LDH (Y/N); PS (0 vs. 1-2). Pts received DTIC 1,000 mg/m(2) Q3 weeks. Patients randomized to GNS received 7 mg/kg/d for 5 days by continuous IV infusion prior to DTIC. Primary endpoint: overall survival (OS). Secondary endpoints: progression-free survival (PFS); response rate (RR, RECIST criteria).