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Background: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and methods: We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. Results: Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). Conclusion: Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Angiosarcoma is a highly aggressive soft tissue sarcoma. Responses to anthracyclines plus/minus ifosfamide, and taxanes alone or in combination with gemcitabine are well documented. Very few data are available on gemcitabine as a single agent.We retrospectively reviewed all cases of advanced progressive angiosarcoma treated with gemcitabine as a single agent (1000 mg/m(2) i.v. every week for 3 weeks every 4 weeks), at Istituto Nazionale Tumori and within the Italian Rare Cancers Network from January 2008 to November 2010.Twenty-five patients [mean age: 52 years; radiation therapy (RT)-related: 8] received gemcitabine. Best tumor response by RECIST was as follows: complete response = 2, partial response = 14, stable disease = 2, progressive disease = 7 cases, for an overall response rate (PR + CR) of 68%. Six of eight post-RT angiosarcomas responded to treatment. Median overall survival (OS) was 17 months. Median progression-free survival (PFS) was 7 months (range 1-40 months). One patient with a locally advanced thyroid angiosarcoma became resectable after 5 months of gemcitabine, with10% residual viable tumor cells seen on surgical specimen. Overall, gemcitabine was well tolerated.Gemcitabine is active in both RT- and non-RT-related angiosarcoma, with dimensional and possibly long-lasting responses. A formal phase II study on gemcitabine as a single agent is warranted.

Background: The expression of ATP-binding cassette transporters on circulating tumor cells (CTCs) is predictive of response to chemotherapy in cancer patients. We tested the hypothesis that drug-resistant CTCs might have predictive value in metastatic breast cancer (MBC) and possibly retain stem-like properties. Patients and methods: CTCs obtained from 42 MBC patients were evaluated for multidrug-resistance-related proteins (MRPs), aldehyde dehydrogenase 1 (ALDH1), estrogen receptor α (ERα) and human epidermal growth factor receptor 2 (HER2/neu). Primary objective was to evaluate the prognostic and predictive value of CTCs profile. Secondary end points were the level of concordance in ERα and HER2/neu status between primary tumors and CTCs and the correlation in CTCs between ALDH1, drug resistance profile and number of MRPs. Results: A difference in progression-free survival (PFS) was found between CTCs-positive and CTCs-negative patients. PFS was shorter in patients with a ‘drug resistance’ CTCs profile and in patients whose CTCs expressed two or more MRPs. No correlation was found between tumor characteristics and ALDH1. ALDH1 correlated to negative ERα and positive HER2/neu status in CTCs. The correlation between the number of MRPs expressed in CTCs and ALDH1 was statistically significant. Conclusion: In MBC, the presence of CTCs expressing MRPs and ALDH1 is predictive of response to chemotherapy.

Background: Capecitabine and gemcitabine given as fixed dose rate (FDR) has not been demonstrated to be well tolerated in phase I previous studies. The goals of this phase I study were to determine the maximum-tolerated dose of this combination and to describe the dose-limiting toxic effects (DLT) and the safety profile of this way of administration. Patients and methods: Patients with advanced solid tumors were eligible for this study. Capecitabine was administered orally at a dose of 650 mg/m2 bis in die (b.i.d.) for 14 consecutive days. Gemcitabine was administered at FDR of 10 mg/m2 per min in escalating durations of infusion on days 1 and 8. The cycles were repeated every 21 days. Results: All 20 patients enrolled into the study were assessable for toxicity. Only one out of the first six patients treated at FDR gemcitabine dose of 800 mg/m2 met protocol-specified DLT criteria (grade 4 neutropenia lasting ≥7 days) during the first two cycles. At these doses the majority of cycles of therapy were, however, delivered without dose reduction or delay. Another similar episode of DLT was observed at the same dose step among the following eight included patients. The dose of FDR gemcitabine 800 mg/m2 in 80 min on days 1 and 8 plus capecitabine 650 mg/m2 b.i.d., for 14 consecutive days followed by 1 week of rest is recommended for further study. Conclusion: The combination of FDR gemcitabine plus capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies.

Background To report the efficacy of induction treatment (IT) protocol with concurrent radiochemotherapy in locally advanced non-small-cell lung cancer (NSCLC), and to analyze downstaging as a surrogate end point. Patients and methods Patients with histo- or cytologically confirmed stage IIIA or IIIB NSCLC were treated according to an IT protocol followed by surgery. Downstaging was assessed for all resected patients. Results In the period between February 1992 and July 2000, 92 patients were enrolled in the study (57 IIIA, 35 IIIB). Response was observed in 63 patients; 56 patients underwent radical resection. Patients downstaged to stage 0–I (DS 0–I) showed a statistically significant improved disease-free survival (26.2 months pStage 0–I versus 11.2 months pStage II–III; P = 0.0116) and overall survival (median 32.5 months pStage 0–I versus 18.3 months pStage II–III; P = 0.025). Patients with DS 0–I had a significantly lower probability (P = 0.0353) of developing distant metastases estimated in 0.2963 odds ratio. Conclusion Neoadjuvant radiochemotherapy is feasible with good pathological DS results. Pathological downstaging was confirmed to have high predictive value. Its use is suggested in the short-term evaluation of induction protocols efficacy in locally advanced NSCLC.