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Metronomic oral chemotherapy (CT) versus the same regimen in association with Thalidomide (TLM): results of a randomized trial in patients (pts) with advanced breast cancer (ABC)

3015 Background: Clinical efficacy and antiangiogenic effect of low dose, continuous oral cyclophosphamide (CTX) and methotrexate (MTX) have been demonstrated. We hypothesized that the addition of TLM might further improve clinical response and modulate angiogenic factors in pts with ABC. METHODS Pts with ABC, either untreated or pretreated, were randomized to receive an oral schedule of MTX (2.5 mg orally, twice daily on day 1 and day 4) and CTX (50 mg, orally, daily) (arm A) or to receive the same regimen plus TLM (200mg, orally, daily) (arm B). Blood samples were collected at first visit and monthly to measure VEGF, bFGF, and circulating endothelial cells. RESULTS 178 pts were enrolled, 166 were evaluable for response. PS was 0 (150 patients), 1 (28 patients). Metastatic sites: lung (40 pts), liver (75 pts), bone (79 pts), lymph nodes (48 pts), and skin (20 pts). Median age was 54 (range 31-78). Progressive disease at study entry reported in 113 pts. Pts were stratified by preatreatment (no = 58; yes = 120). In the latter, 75 pts were pretreated with 1 line of CT, 45 pts with ≥ 2. Three CR in arm A and 4 in arm B, 17 PR in arm A and 9 in arm B for an overall response of 24% in arm A e 16% in arm B, SD was seen in 29 pts in arm A and 31 in arm B. The overall clinical benefit (CR+ PR+ SD >24 weeks) was 47% for both arms. PD was observed in 41% of pts in arm A and in 47% of pts in arm B. Overall clinical toxicity was generally mild. Grade ≥2 leucopenia was reported in 39 pts. Grade ≥2 thrombocytopenia appeared in 4 pts. Grade ≥2 liver toxicity was reported in 59 pts. No difference in terms of toxicity were observed between the 2 arms, with exception of more neurological toxicity (grade ≥2) and higher incidence of thromboembolic events in the TLM arm. In arm B twelve pts (14%) stopped TLM: 8 due to neurological toxicity grade 1-2, 2 due to hematological toxicity, 2 due to skin toxicity. Two pts in Arm B had a Grade 4 pancytopenia (1) and thromboembolism (1). CONCLUSIONS Adding TLM to continuous, low-dose CTX and MTX did not increase clinical responses in pts with ABC. No significant financial relationships to disclose.

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3–4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0–1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0–1, Odds Ratio 25.8, p 0.049. AJCC grade 0–1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Noninferiority of three months versus six months of oxaliplatin-based adjuvant chemotherapy for resected colon cancer. How should IDEA findings affect clinical practice?: How should IDEA findings affect clinical practice?

The eagerly awaited results of the multi‐continental International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project have recently been presented at major oncological meetings. The 3‐year disease‐free survival (DFS) was presented for 12,834 Stage III colon cancer patients in a pooled analysis of 6 individual noninferiority phase III randomized trials, all investigating three versus six months of oxaliplatin‐based adjuvant therapy. Noninferiority (NI) could not be demonstrated for the whole population as the DFS hazard ratio (HR) of 1.07 with its 95% CI of 1.00–1.15 crossed the postulated NI boundary of 1.12. However, there was an expected reduction in the incidence of specific side effects with the three months treatment. NI could be demonstrated for the T3N1 subgroup (∼60% of patients, HR for DFS 1.01, 95% CI 0.90–1.12). Moreover, NI was also declared for the subgroup treated with the CAPOX regimen (capecitabine plus oxaliplatin, ∼40% of patients), but the CAPOX choice was physician‐based and not subject to randomization. Overall, the IDEA results indicate that three months of therapy might be adequate for most of Stage III tumors; however, a small subset of these patients still have high risk of recurrence and death with short treatment duration. Precise predictors of benefit need to be identified, nonetheless tumor‐intrinsic factors, such as tumor stage, might currently be considered as useful tools to inform the decision‐making process.

BMI and health-related quality of life (HR-QoL) in patients with metastatic colorectal cancer (mCRC).

249Background: Relationship between BMI and HR-QoL has been extensively studied in CRC survivors. Increasing BMI has been recently associated with improved survival in mCRC pts, however data on the relationship between BMI and common HR-QoL measures in mCRC are scarce Methods: The EORTC QLC C30 and the NCCN distress thermometer (DT) and problem list (PL) questionnaires were administered to consecutive mCRC pts candidate for firstline chemotherapy. The effect of BMI on HR-QoL were analyzed using the Kruskal-Wallis and Mann-Whitney tests. The interaction between BMI and other variables of interest (such as inflammatory indexes) for the effect on HR-QoL was also analysed using a logistic regression analysis Results: Of 135 screened pts, 119 completed the questionnaires. A direct association was observed between BMI and GH score, with the score gradually improving from BMI 14 to 21, then plateauing between 21 and 41. A significantly lower GH was observed for BMI 21 (GH 50 vs 67, p 0.014). DT and BMI...

Gender Differences in Cancer-Associated Venous Thromboembolism.

Venous thromboembolism (VTE) is a commonly diagnosed multifactorial condition with significant morbidity and mortality, occurring in up to 20% of cancer patients. Indeed, patients with cancer are in a higher pro-thrombotic state due to alterations in their haemostatic- coagulative system, stasis and blood flow slowdown, endothelial dysfunction, vascular inflammation and platelet activation. Moreover, several cancer-dependent factors can sum up to trigger a first episode of VTE or to cause its recurrence in the course of anticoagulant treatment. Such a pro-thrombotic condition is further worsened by additional favoring risks such as immobilization, infection, surgery, or insertion of a central venous catheter, and anti-cancer therapy. Furthermore, in the secondary prevention setting, the anticoagulant therapy is accompanied by a high incidence of bleeding complications. Given the above, understanding and identifying the factors associated with the incidence and clinical outcome of VTE in cancer patients might be of great value in the prevention and management of VTEattributable complications, including death. Differences associated to gender on cancerrelated VTEs are not yet fully defined; many of the studies that addressed the question have been biased by erroneous/non homogeneous inclusion criteria. In the present review, we analyzed the potential differences in VTEs occurrence in cancer patients, by reporting the most significant findings in the recent literature. The identification of a differential clinical approach according to patient sex, might prompt the design of personalized treatment options tailored and optimized according to algorithms for oncological VTE prevention.