3558 Purpose: Recent data have demonstrated in preclinical tumor models an antiangiogenic and antitumor activity of low weekly doses of ZA. As a consequence, the purpose of this study was to confirm these data, evaluating in cancer patients the modifications in angiogenic cytokines levels following repeated weekly low doses of ZA. Experimental Design: 26 consecutive cancer patients with bone metastases treated, for the first time, with four weekly doses of 1 mg of ZA followed by standard doses (4 mg every 28 days) were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) at different time points: just before and after 1, 7, 14, 21, 28, 56 and 84 days following the first disphosphonate infusion. Results: Basal serum VEGF median levels were significantly decreased just after 7 days (-29.7%) (with only one weekly infusion) (P=0.038), This significant decrease of circulating VEGF levels persisted 14(-33.2%), 21 (-39.4%), 28(-31.8%), 56(-33.6%) and 84(-27.9%) days after the first infusion (respectively, P=0.002, P=0.001, P=0.008, P=0.002, P=0.014). Conclusions: This study confirms, for the first time in humans, that weekly low doses of zoledronic acid could have antiangiogenic properties through a significant and long lasting decrease of VEGF serum levels. No significant financial relationships to disclose.

12016 Background: Combination of C and G has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. To determine the toxicity of C plus Fixed Dose Rate (FDR) G in metastatic cancer patients, a phase I trial was conducted. Methods: This is an open-label, single-center, dose-escalating phase I study. C was administered orally according to the standard 21-day schedule: bid in equal doses (650 mg/m2 bid) for 14 days every 21 days. G was administered at a FDR of 10 mg/m2 per min in escalating durations of infusion on days 1 and 8 every 21 days. The doses of G explored were 600, 700, 800 mg/m2 infused at FDR in 60, 70 and 80 minutes, respectively. 15 pts (10 female, 5 male), aged 37–70 yr (median 66) with a variety of advanced solid tumors have been treated (11 peri-ampullary cancers, 3 colorectal cancers and 1 ovarian cancer). The FDR G dose was escalated when 3 patients in a cohort had completed two cycles of treatment without experiencing dose-limiting toxicities (DLT). The MTD was defined as the dose level at which no more than one of nine patients experienced a DLT. Results: No DLT occurred at doses of 600 and 700 mg/m2 in any of the 3 patients included at each level. At 800 mg/m2, 1 of 9 patients experienced DLT (neutropenia grade 4 with fever). The non-haematological toxicities have been generally mild or moderate in all patients (grade 2 stomatitis: 4 patients; grade 2 fatigue: 3 patients; grade 2 nausea/vomiting: 2 patients). 2 patients showed one episode of grade 4 neutropenia spontaneously regressed in 3 days. 2 patients showed one episode of grade 2 thrombocytopenia. The recommended dose for further studies is C bid in equal doses (650 mg/m2 bid) for 14 days (28 doses) plus FDR G at 800 mg/m2 infused in 80 minutes on days 1 and 8 every 21 days. Other patients with periampullary carcinoma are being evaluated at the same dose level, with an ongoing evaluation of cumulative (all cycles) toxicity and efficacy. In terms of response, we have observed 2 PR and 3 SD in the 6 pancreatic cancer patients evaluated for response after the first 3 cycles. Conclusions: C plus FDR G combination seems to be a feasible and safety approach which has demonstrated promising clinical activity. No significant financial relationships to disclose.

3706 Background: We retrospectively evaluated the relevance of TS expression and DPD in normal colonic mucosa as predictive factors of toxicity in colorectal cancer patients receiving adjuvant 5-FU based chemotherapy. Methods: TS and DPD expression were immunohistochemically assessed on normal colonic mucosa from 64 patients with colorectal cancer Dukes’ stages B (35 patients) and C (29 patients) treated with 5-fluorouracil (5-FU) based adjuvant chemotherapy. Results: The incidence of grade 2–3 diarrhoea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (P<0.0001). Moreover, patients with low DPD expression in normal colonic mucosa developed more commonly grade 2–3 diarrhoea (55% vs 23%, p=0.062) and stomatitis (48% vs 23%, p=0.013). Furthermore, considering the concomitant expression of TS and DPD, we identified three groups of patients (group 1: TS + and DPD +, group 2: TS - and DPD -, group 3: only one +). The incidence of grade 2–3 diarrhoea and stomatitis were statistically significant higher in group 2 than in groups 1 and 3 (diarrhoea; 76% vs 24%, P<0.0001; stomatitis: 76% vs 24%; P<0.0001). Conclusions: Immunohistochemical TS and DPD expression in normal colonic mucosa and their combination, may represent two important predictive parameters for identifying a subset of patients with high risk of developing severe 5FU- related toxicities. No significant financial relationships to disclose.

Objectives: We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy. Methods: TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes’ stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy. Results: The incidence of grade 2–3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation. Conclusions: Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities.

AllergyVolume 59, Issue 2 p. 241-241 Anaphylaxis to dexrazoxane (ICRF-187) following three previous uncomplicated infusions V. Leoni, V. Leoni Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorD. Santini, D. Santini Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorB. Vincenzi, B. Vincenzi Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorC. Grilli, C. Grilli Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorN. Onori, N. Onori Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorG. Tonini, G. Tonini Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this author V. Leoni, V. Leoni Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorD. Santini, D. Santini Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorB. Vincenzi, B. Vincenzi Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorC. Grilli, C. Grilli Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorN. Onori, N. Onori Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this authorG. Tonini, G. Tonini Università Campus Bio-Medico Via Emilio Longoni, 83 00155 Rome Italy E-mail: [email protected]Search for more papers by this author First published: 03 February 2004 https://doi.org/10.1046/j.1398-9995.2003.00383.xCitations: 2 We describe the case of a breast cancer patient who developed dexrazoxane-induced anaphylaxis. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Von Hoff DD. Phase I trials of dexrazoxane and other potential applications for the agent. Semin Oncol 1998; 25: 31–36. 2 Vogel CL, Gorowski E, Davila E, Eisenberger M, Kosinski J, Agarwal RP et al. Phase I clinical trial and pharmacokinetics of weekly ICRF-187 (NSC 169780) infusion in patients with solid tumors. Invest New Drugs 1987; 5: 187–198. 3 Von Hoff DD, Howser D, Lewis BJ, Holcenberg J, Weiss RB, Young RC. Phase I study of ICRF-187 using a daily for 3 days schedule. Cancer Treat Rep 1981; 65: 249–252. 4 Seymour L, Bramwell V, Moran LA. Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer: The Provincial Systemic Treatment Disease Site Group. Cancer Prev Control 1999; 3: 145–159. Citing Literature Volume59, Issue2February 2004Pages 241-241 ReferencesRelatedInformation

Colorectal cancer represents a major health problem in the western world. A lot of drugs have been employed in treatment of this disease, but only few data are available about predictive factors for response to anticancer treatments in colorectal cancer. Aim of this paper is to review the main data about this investigation field. Using a Medline database search (1966-2003) we reviewed all the relevant papers that investigate clinical and molecular predictors for response to the main drugs used in the treatment of colorectal cancer patients, both in adjuvant and in advanced setting. Moreover we comprehensively reviewed all the data published in abstract form during the most significant international meetings. Our review put in evidence the most important predictive factors for response in colorectal cancer patients treated with anticancer chemotherapy both in adjuvant and in advanced setting. The predictive factors are clustered on the basis of the different anticancer drugs. The results of this review provide the rationale basis for personalizing anticancer treatment in colorectal cancer patients by molecular and clinical features, aiming to improve response rate and reduce toxicities.