Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.

The results indicate that UGT1A1*28 polymorphism is of some relevance to toxicity; however, it is less important than discussed in previous smaller trials. In particular, the possibility of a dose reduction for irinotecan in patients with a UGT1A1*28 polymorphism is not supported by the result of this analysis.

PurposeA previous randomized clinical trial by the Italian Sarcoma Group (ISG) had shown a survival benefit of adjuvant chemotherapy (CT) in high-risk extremity soft tissue sarcoma (STS). However, the dose-intensity of the last two cycles was suboptimal. We then undertook a multicentric international phase III study to compare three and five cycles of the same CT.Patients and MethodsPatients were randomly assigned either to receive three cycles of preoperative CT with epirubicin 120 mg/m2and ifosfamide 9 g/m2and granulocyte colony-stimulating factor (arm A) or to receive the same three cycles of preoperative CT followed by two further cycles of postoperative CT (arm B). Noninferiority of the primary end point, overall survival (OS), was assessed by the CI of the hazard ratio (HR; arm A/arm B) obtained from the Cox model.ResultsBetween January 2002 and April 2007, 328 patients were recruited (164 patients in each arm). At a median follow-up of 63 months (interquartile range, 49 to 77 months), 100 deaths were recorded, 49 in arm A and 51 in arm B. Five-year OS probability was 0.70 for the entire group of patients (0.68 in arm A and 0.71 in arm B). The HR of arm A versus arm B was 1.00 (90% CI, 0.72 to 1.39).ConclusionIn this population of patients with high-risk localized STS, three cycles of full-dose preoperative CT were not inferior to five cycles. The outcome compares favorably with the expected survival of patients with high-risk STS and was superimposable on the CT arm of the previous ISG trial.

Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56–119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).

BACKGROUND The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first‐line treatment in metastatic colorectal carcinoma (CRC). METHODS A total of 140 patients received capecitabine at a dose of 1250 mg/m2 twice daily on Days 2–15 and irinotecan at a dose of either 300 mg/m2 on Day 1 (Arm A) or 150 mg/m2 on Days 1 and 8 (Arm B) every 3 weeks. During the course of the study, enrollment was continued using lower doses of capecitabine (1000 mg/m2 twice daily) and irinotecan (Arm A: 240 mg/m2; Arm B: 120 mg/m2) to improve the safety profile of the combinations. RESULTS Efficacy was evaluable in 134 patients (68 in Arm A, 66 in Arm B). Objective responses were observed in 46% of the patients (8% complete response [CR]), including 47% in Arm A (9% CR; 38% partial response [PR]) and 44% in Arm B (8% CR; 36% PR). The median progression‐free survival was 8.3 months in Arm A and 7.6 months in Arm B. Among the first 52 patients treated with the higher doses, the most frequent Grade 3–4 adverse event was diarrhea (27%). The lower doses adopted in the subsequent 88 patients led to better diarrhea control, particularly in Arm A, and significant reductions in the incidence of all‐grade hand‐foot syndrome and abdominal pain. CONCLUSIONS The capecitabine and irinotecan combination was a highly active first‐line therapy in metastatic CRC. An acceptable safety profile was observed after dose reduction, particularly when irinotecan was administered on 1 day. Cancer 2004;100:279–87. © 2003 American Cancer Society.

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PurposeA phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.MethodsThis multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25 mg intravenously) and dexamethasone (8 mg intravenously) before chemotherapy, while the other was administered the same regimen on day 1 followed by dexamethasone 8 mg orally on days 2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days 1–5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.ResultsOf 332 chemotherapy-naïve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day 1 (n = 166), and 71.1% for those also administered dexamethasone on days 2 and 3 (n = 166; difference −3.6% (95% confidence interval, −13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0–24 h post-chemotherapy; 88.6% versus 84.3%; P = 0.262) and delayed phases (days 2–5; 68.7% versus 77.7%; P = 0.116).ConclusionsPalonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3 days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.

Preoperative chemoradiation with capecitabine and RT appeared to be effective in locally advanced resectable, rectal cancer. The favorable safety profile of the combination might warrant the use of capecitabine and RT with other effective new drugs.