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| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 Jan 1. pii: 10.1200/jco.2004.22.14_suppl.3509 |
| Capecitabine (X) vs bolus 5-FU/leucovorin (LV) as adjuvant therapy for colon cancer (the X-ACT study): positive efficacy results of a phase III trial. |
| Cassidy J1, Scheithauer W2, McKendrick J3, Kröning H4, Nowacki MP5, Seitz JF6, Twelves C7, Van Hazel G8, Wong A9, Díaz-Rubio E10 |
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Abstract 3509 Background Treatment with capecitabine (XELODA), a tumor-activated oral fluoropyrimidine, led to significantly superior response rates and improved safety over bolus 5-FU/LV in 1(st)-line metastatic colorectal cancer patients. MethodsPatients with resected Dukes' C colon cancer were randomized to oral X (1250 mg/m(2) twice daily days 1-14, every 3 weeks) or i.v. 5-FU/LV (Mayo Clinic regimen: LV 20 mg/m(2) 5-FU 425 mg/m(2) days l-5, every 4 weeks) for 24 weeks' treatment. The primary endpoint was at least equivalence in disease-free survival (DFS). Results A total of 1987 patients from 164 centers were randomized between 11/98 and 11/01. The arms were well balanced for prognostic factors. Median follow-up is 3.8 years. The primary endpoint of the study was met. X was at least equivalent to 5-FU/LV with regard to DFS in the per protocol population (HR 0.89 [95% CI 0.76-1.04]). In the intent to treat (ITT) analysis there was a strong trend towards superior DFS for X vs 5-FU/LV (HR 0.87 [95% CI 0.75-1.00], p = 0.0528), and a trend to superiority for overall survival (OS; ITT: HR 0.84 [95% CI 0.69-1.01], p = 0.0706). Relapse-free survival (RFS) was superior for X vs 5-FU/LV (ITT: HR 0.86 [95% CI 0.74-0.99], p = 0.041). The results seen in the entire population were maintained in patients ≥ 70 years. The favorable safety profile of X compared to 5-FU/LV has been described earlier (Scheithauer, Ann Oncol 2003;14:1735-43). Conclusion The primary endpoint of the study was met. The trend to superiority in DFS and OS, supported by superior RFS and safety mean that X should replace 5-FU/LV in the adjuvant therapy of colon cancer. [Table: see text]. METHODS: Patients (pts) with biopsy proven breast cancer T1-4a-c,N /-,M0 were eligible for this prospectively randomized phase III trial. 282 pts (estimated drop-out rate: 5%) were planned to detect a significant difference (one-sided p < 0,05, Fisher's exact test) with a power of 82%. Pts were randomized to receive either 3 cycles of epirubicin 75mg/m(2) and docetaxel 75mg/m(2) on day 1 G-CSF 30 MU days 3-10 q 21 days (ED G) or 6 cycles of the identical regimen. Primary end point was the rate of pCR. The pathological nodal status and the rate of breast conserving surgical procedures served as secondary end points. RESULTS: 292 pts were accrued to the trial between 6/199 and 12/2002 and 288 pts are eligible. Both trial groups were well balanced for tumor size, clinical nodal status, menopausal status, hormone receptor status, HER2-status, and trial center. The results of the primary and the secondary end points are depicted in the table. There was no significant difference in serious adverse events per patient and per cycle and no patient died while on treatment. [Figure: see text] Conclusions: Doubeling the number of cycles of neoadjuvant chemotherapy (6 vs. 3 x ED G) results in significantly higher rates for pCR and negative axillary nodal status with with no excess of side effects. [Table: see text]. CONCLUSIONS: Adjuvant chemotherapy with oral X yields substantial savings in MRU due to the avoidance of administration costs of i.v. 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]. |
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Publikations ID: 28016480 Quelle: öffnen |
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