Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Background:The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). Results:The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months). Conclusion:Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI. metastases but also in the context of disease management with regard to improving the quality of life and lengthening the survival of nonresectable patients. For many years, 5-fluorouracil (5-FU), generally combined with the biological response modifier folinic acid (FA) [4], has been the mainstay of treatment regimens for mCRC, with meta-analyses suggesting that infusional delivery is more effective [5] and associated with less grade 3/4 hematological toxicity than bolus administration [6]. The introduction of two further cytotoxic chemotherapy agents, irinotecan and oxaliplatin, have more recently allowed the development of multiline combination therapy for mCRC patients. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Group and others were able to demonstrate that median survival times of >20 months are now achievable [7,8], with the use of three active drugs during the course of a patient's treatment conferring maximum survival benefit [9]. It is anticipated that the use of targeted biological agents in this setting will further improve the performance of existing cytotoxic therapies [10].Currently, infusional 5-FU/FA combined with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) are regarded as standard first-line chemotherapy regimens of equivalent efficacy. The devices used during the infusion process may be associated with infection or thrombosis [11]. One possible solution to this problem might be the oral delivery of fluorouracil. Capecitabine is an inactive oral prodrug which is preferentially enzymatically converted in tumors to fluorouracil [12]. Although there are no reported studies comparing the safety and efficacy of capecitabine with infusional 5-FU, the oral prodrug has been shown to be less toxic and at least as effective as the Mayo Clinic bolus 5-FU regimen [13,14]. As combination therapy is now the first-line treatment of choice for most mCRC patients, opportunities to formally compare the efficacy and safety of infusional 5-FU/FA monotherapy versus capecitabine monotherapy are limited. Such informat...

The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.

Dose-dense temozolomide schedules deplete O6-methylguanine methyltransferase and may overcome chemoresistance. This multicenter cohort study enrolled 19 patients (15 anaplastic astrocytoma, 4 anaplastic oligoastrocytoma) who received temozolomide (100 mg/m2/day for 21 consecutive days every 28-day cycle) at first recurrence, either until disease progression or 12 cycles. Six-month progression-free survival was 56%, comparing favorably with historic controls treated with the standard 5-day temozolomide schedule. Median survival was 12.9 months (95% CI: 3.7, 22 months). Among 15 evaluable patients, 2 had a complete or partial response, and 10 had stable disease. Grade 3 and 4 lymphopenia occurred in 53% and 47% of patients, respectively.

Although irinotecan 350 mg m À2 is a standard option for relapsed/refractory advanced colorectal cancer, there is some evidence that suggests that a higher dose may be more effective, with acceptable tolerability, following 5-fluorouracil (5-FU). This study assessed the optimal dosing strategy for irinotecan, along with treatment efficacy and safety. A total of 164 patients with metastatic colorectal cancer progressing after failure on 5-FU or raltitrexed received either 350 mg m À2 irinotecan (Group A; n ¼ 36) or 250, 350 or 500 mg m À2 , according to individual patient tolerance (Group B; n ¼ 62) or based on risk factor optimisation (Group C; n ¼ 66). There were no complete responses. There was a trend towards a higher overall response rate in Group B (13%) than in Groups A (8%) and C (9%). Tumour control growth rate was high in all three groups: 58% in group A, 60% in Group B and 50% in Group C. A total of 34% of patients in Group B and 9% in Group C were able to receive a dose of 500 mg m À2 . Median duration of response and time to progression were significantly longer in Groups A and B compared with Group C. No significant between-group differences for any adverse events were seen, although there was a small trend towards better tolerability in Group B. Individual dose escalation based on patient tolerance may allow more patients to receive a higher irinotecan dose without causing additional toxicity and can be an appropriate patient management strategy. 1999). Median overall survival rates of up to 10 months are achievable when irinotecan is used in relapsed/refractory colorectal cancer (Shimada et al, 1993; Rothenberg et al, 1996 Rothenberg et al, , 1999Pitot et al, 1997;Rougier et al, 1997;Van Cutsem et al, 1999). Two European phase III trials investigating the efficacy and safety of irinotecan, following 5-FU failure in advanced colorectal cancer, have demonstrated significant improvements in survival compared with best supportive care and 5-FU (Cunningham et al, 1998;Rougier et al, 1998). The main adverse events accompanying treatment with irinotecan in these trials were diarrhoea, neutropenia, fatigue, nausea and vomiting.Although 350 mg m À2 as an intravenous infusion every 3 weeks is the standard recommended dosage of irinotecan, pharmacokinetic parameters of irinotecan-lactone and the active metabolite SN-38-lactone vary between individuals (Xie et al, 2002). This may be attributed to differences in the levels of the enzymes that metabolise irinotecan, notably carboxylesterase for SN-38. Furthermore, the variable interindividual patient exposure to SN-38 has been identified as an important determinant of toxicity .At the same time, there is convincing evidence of a doseresponse relationship, and therefore a rationale for increasing doses when possible. In a phase I trial by Abigerges et al (1995), there were two recommended doses: 350 mg m À2 without highdose loperamide and 600 mg m À2 with high-dose loperamide. With the exception of one responder treated at 260 mg m À2 , all objective responses...