Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial.

Background: We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy.

Patients And Methods: This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC.

Efficacy and tolerability of biweekly bevacizumab, irinotecan, folinic acid and fluorouracil intravenous bolus (BIFF Regimen) in patients with metastatic colorectal cancer: the southern Italy cooperative oncology group experience.

Background: We have extensively assessed a biweekly regimen of irinotecan plus folinic acid and fluorouracil bolus (IRIFAFU) in metastatic colorectal cancer (MCRC). Here, we report on the safety and activity of BIFF (bevacizumab plus IRIFAFU) regimen in 94 mCRC patients.

Patients And Methods: Bevacizumab 5 mg/kg (1 hour), and irinotecan 180 mg/m(2) (1 hour) were given intravenously on day 1, 6S-folinic acid 250 mg/m(2) (2 hours), and fluorouracil 850 mg/m(2) (bolus) were given intravenously on day 2 every 2 weeks for a median of 9 cycles per patient (range, 1-12), and maintenance bevacizumab alone was delivered in 16 cases.

Molecular analysis of Fanconi anemia and mismatch repair genes in patients with colorectal carcinoma.

A cohort of 206 consecutively-collected patients with colorectal carcinoma (CRC) were screened for germline mutations in the principal DNA mismatch repair (MMR) genes, MLH1 and MSH2, and in the Fanconi anemia (FA) genes involved in homologous recombination DNA repair. Mutation analysis was performed by denaturing high-performance liquid chromatography (DHPLC) and automated sequencing. Available paraffin-embedded tumor tissues were evaluated for gene expression by immunohistochemistry.

Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term outcome.

Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma.

Methods And Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m2; raltitrexed (RTX), 2.5 mg/m2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m2 (31 patients) or 800 mg/m2 (32 patients); levo-folinic acid (LFA), 250 mg/m2 on day 2, during pelvic RT (45 Gy).

Baseline physical functioning status of metastatic colorectal cancer patients predicts the overall survival but not the activity of a front-line oxaliplatin-fluoropyrimidine doublet.

Background: No differences in response rate (RR), progression-free survival (PFS), overall survival (OS) and quality of life (QoL) were seen in patients randomly treated with biweekly oxaliplatin plus either fluorouracil/folinic acid or capecitabine.

Methods: We investigated the independent effect of baseline clinical characteristics and physical functioning (PF) domain on RR, PFS, and OS in 310 patients who completed the EORTC QLQ-C30 questionnaire. Multivariate analyses stratified by treatment were performed.

Optimizing the management of metastatic colorectal cancer.

The prognosis of patients with metastatic colorectal cancer has significantly improved in the last few years, with the introduction into the clinical practice of new cytotoxic treatments, the availability of non-cross resistant agents after the front-line treatment failure, and the combination of targeted agents (i.e., the inhibitors of the epidermal growth factor and vascular endothelial growth factor pathways) with conventional drugs.

Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer: a randomized phase II SICOG trial.

Purpose: To estimate the safety, activity, and impact on quality of life of a combination of gemcitabine and pemetrexed in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in the context of a randomized two-stage phase II study.

Patients And Methods: Patients in stage IIIB or IV NSCLC were randomly allocated to receive either gemcitabine 1250 mg/m(2) on day 1, and pemetrexed (Alimta) 500 mg/m(2) followed by gemcitabine 1250 mg/m(2) on day 8 of a 3-weekly cycle (GA arm), or paclitaxel 120 mg/m(2) followed by gemcitabine 1000 mg/m(2), both given on days 1 and 8 of a 3-weekly cycle (PG arm).

Results: 105 (GA arm, 51; PG arm, 54) eligible patients (stage IV, 32 and 30, respectively) were enrolled into this study; thereafter, accrual was stopped due to first-stage analysis.

Role of oxaliplatin in the treatment of colorectal cancer.

Oxaliplatin is a third-generation platinum compound that has shown a definite role in the management of colorectal cancer (CRC). Oxaliplatin in combination with fluorouracil and leucovorin in the FOLFOX4 regimen represents a new standard of treatment in the adjuvant setting as well as for the metastatic disease. The combination of oxaliplatin with capecitabine in the XELOX regimen has been demonstrated to be not inferior to FOLFOX4 in metastatic patients, and it is under evaluation, with or without bevacizumab, in the post-surgical management of resected patients.

Emerging role of capecitabine in gastric cancer.

For many years, a regimen of fluorouracil and cisplatin has been the standard of care for the treatment of patients with metastatic gastric cancer. More recently, triplet regimens that incorporate fluorouracil and cisplatin with epirubicin (ECF) or docetaxel are being used in the management of patients with metastatic disease; ECF is also being used as preoperative treatment of resectable disease. Capecitabine, a prodrug of fluorouracil that can be taken orally, has been assessed as an alternative to intravenous fluorouracil and has demonstrated noninferiority to its parent compound.

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group.

Purpose: This phase II trial assessed the tolerability and efficacy of a triplet of oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer.

Methods: Patients with unresectable or metastatic gastric cancer, unexposed to palliative chemotherapy, received oxaliplatin 85 mg/m(2) iv and irinotecan 150 mg/m(2) iv on day 1, 6S-folinic acid 250 mg/m(2) iv and fluorouracil 750 mg/m(2) iv on day 2, every 2 weeks. Response rate (RR) was assessed after a minimum of four cycles, and treatment continued up to 12 cycles.

Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401.

Purpose: Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients.

Methods: A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.

A review of the role of capecitabine in the treatment of colorectal cancer.

5-fluorouracil/leucovorin, with or without oxaliplatin or irinotecan, is the most widely used treatment for the metastatic as well for the adjuvant setting of colorectal cancer. These agents are administered intravenously (by bolus or infusion), thereby causing significant inconvenience to patients. Capecitabine, an oral fluoropyrimidine, has been demonstrated to be at least as effective as bolus 5-fluorouracil/leucovorin in terms of time to disease progression, time to treatment failure, and overall survival, but achieves significantly higher response rates and has the advantage of oral administration.

Capecitabine, alone and in combination, in the management of patients with colorectal cancer: a review of the evidence.

Capecitabine, an oral prodrug of fluorouracil (5FU), has shown efficacy in terms of progression-free and overall survival at least equivalent to standard folinic acid (leucovorin)-modulated intravenous 5FU bolus regimens in patients with metastatic colorectal cancer. Moreover, capecitabine has demonstrated a better tolerability profile, producing a significantly lower occurrence of severe stomatitis than 5FU plus folinic acid regimens, making this drug particularly attractive for treating elderly patients. In addition, capecitabine can be combined with other active drugs such as irinotecan or oxaliplatin.

Comparison of the safety and efficacy of paclitaxel plus gemcitabine combination in young and elderly patients with locally advanced or metastatic non-small cell lung cancer. A retrospective analysis of the Southern Italy Cooperative Oncology Group trials.

We retrospectively assessed tolerability and efficacy of paclitaxel plus gemcitabine combination in 259 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) enrolled in three randomized SICOG trials according to their age (70 years) at study entry. Apart from age, demographic and clinical characteristics were similar in the two groups. Response rate of paclitaxel plus gemcitabine was similar in younger and in elderly (36% versus 30%).

Synergistic antitumour effect of raltitrexed and 5-fluorouracil plus folinic acid combination in human cancer cells.

5-Fluorouracil, usually in combination with folinic acid, is widely used in the treatment of both colorectal and head and neck squamous cell cancer patients. Since 5-fluorouracil plus folinic acid and the antifolate thymidylate synthase inhibitor; raltitrexed have distinct mechanisms of action and toxicity profiles, we have evaluated the potential synergistic antitumor interaction between these two agents combined with a sequential schedule of administration in KB (wt-p53) and Cal27 (mut-p53) head and neck squamous cell carcinomas, and LoVo (wt-p53) and HT29 (mut-p53) colorectal cell lines. The combination between a 24-h exposure to raltitrexed followed by a 4-h exposure to 5-fluorouracil plus folinic acid was globally synergistic, as assessed by the median effect principle and combination index.

Intra-patient alternated dose escalation of paclitaxel and gemcitabine versus paclitaxel followed by fixed dose rate infusion of gemcitabine in fit elderly non-small cell lung cancer patients. A Southern Italy Cooperative Oncology Group randomised phase II trial.

Purpose: This study was undertaken to select the best schedule of administration for the paclitaxel plus gemcitabine combination in fit elderly patients affected by locally advanced or metastatic non-small cell lung cancer (NSCLC).

Patients And Methods: Ninety-eight patients in stage III or IV NSCLC, aged 70 years or more and in ECOG performance status (PS) View Article and Find Full Text PDF

Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer.

Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial.

18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer.

Unlabelled: 18F-FDG PET is a useful tool for assessing the effects of chemo- or radiotherapy. The aim of this study was to correlate the change in tumor 18F-FDG standardized uptake value (SUV) during and after preoperative radiochemotherapy, with the pathologic response achieved in locally advanced rectal cancer (LARC) patients.

Methods: Thirty-three patients with LARC underwent total mesorectal excision after preoperative treatment, including 3 cycles of oxaliplatin, raltitrexed, 5-fluorouracil, and folinic acid during pelvic radiotherapy (45 Gy).

Real-time contrast-enhanced specific ultrasound in staging and follow-up of splenic lymphomas.

From January 2003 to April 2005 we studied 25 lymphoma patients (10 with HD, 4 with low-grade NHL, 6 with high-grade NHL and 5 with chronic lymphatic leukaemia; 14 men, 11 women, age range 28-79 years). After a baseline US study we rapidly injected 4.8 mL of the second-generation microbubble contrast agent SonoVue (Bracco, Italy).

Safety and efficacy of irinotecan plus high-dose leucovorin and intravenous bolus 5-fluorouracil for metastatic colorectal cancer: pooled analysis of two consecutive southern Italy cooperative oncology group trials.

Background: A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin (LV) 250 mg/m2 plus 5-fluorouracil (5-FU) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer (CRC).

Patients And Methods: Individual data of 254 patients were merged, and baseline features potentially affecting overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of severe toxicity were analyzed by univariate and multivariate analyses.

Results: In the pooled series, ORR was 33% (95% confidence interval [CI], 27%-39%).

Phase I study of temozolomide and lomustine in the treatment of high grade malignant glioma.

Systematic reviews and meta-analysis have demonstrated an improved prognosis by chemotherapy of malignant glioma patients. The effects of clinical research therefore have the aim to find more active drugs or new combination therapies. The combination of Temozolomide (TMZ) and nitrosoureas was evaluated preclinically with an evidence of therapeutic synergy.

Biweekly docetaxel-irinotecan treatment with filgrastim support is highly active in antracycline-Paclitaxel-refractory breast cancer patients.

Purpose: To evaluate the feasibility and activity of combination treatment with docetaxel (DTX) and irinotecan (CPT-11), given together every other week, combined with filgrastim support, in anthracycline- and paclitaxel-pretreated breast cancer (BC) patients.

Patients And Methods: Advanced BC patients pretreated with anthracycline- and paclitaxel-based chemotherapy were eligible. DTX (80 mg/m2) and CPT-11 (100 mg/m2) were given biweekly with filgrastim support (300 microg/day on days 4-7).

Weekly dose-dense cisplatin-epirubicin-paclitaxel administration with granulocyte colony-stimulating factor support does not substantially improve prognosis in extensive disease small-cell lung cancer. A SICOG phase II study.

Purpose: The present study was aimed at defining the antitumor activity of the cisplatin-epirubicin-paclitaxel (PET) weekly administration with granulocyte colony-stimulating factor (G-CSF) support in chemonaive small-cell lung cancer patients with extensive disease (ED-SCLC).

Methods: Chemonaive ED-SCLC patients received cisplatin 30 mg/sqm, epirubicin 50 mg/sqm and paclitaxel 120 mg/sqm, weekly, with G-CSF (5 microg/kg from day 3 to 5) support, for a maximum of 12 weeks.

Results: Thirty-nine patients were treated, for a total of 354 cycles delivered.

Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108.

Background: In patients with metastatic colorectal carcinoma (MCC), capecitabine has demonstrated a superior response rate (RR), equivalent disease progression-free (PFS) and overall survival (OS), and an improved overall tolerability profile compared with bolus 5-fluorouracil/leucovorin (5-FU/LV). The FOLFOX4 regimen, combining oxaliplatin with LV and bolus plus infusional 5-FU (LV5FU2), has been shown to improve RR and PFS versus LV5FU2, and it was more effective and less toxic than irinotecan plus bolus 5-FU/LV. Capecitabine (an oral fluoropyrimidine) may be an effective, well tolerated, and more convenient alternative to 5-FU/LV in combination with oxaliplatin, especially in older patients.

A tailored regimen including capecitabine and oxaliplatin for treating elderly patients with metastatic colorectal carcinoma Southern Italy Cooperative Oncology Group trial 0108.

From September 2001 to November 2002, 35 patients aged 70-81 (median, 75) years, with measurable metastatic lesions from colorectal carcinoma, were treated with a combination of oxaliplatin (OXA) infused i.v. over 2 h on day 1, and capecitabine, assumed orally twice a day (12-h apart) from day 2 to day 15.