Author Correction: Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy.

Polymorphisms contribute to inter-individual differences and show a promising predictive role for chemotherapy-related toxicity in colon cancer (CC). TOSCA is a multicentre, randomized, non-inferiority, phase III study conducted in high-risk stage II/stage III CC patients treated with 6 vs 3 months of FOLFOX-4 or XELOX adjuvant chemotherapy. During this post-hoc analysis, 218 women and 294 men were genotyped for 17 polymorphisms: TYMS (rs34743033, rs2853542, rs11280056), MTHFR (rs1801133, rs1801131), ERCC1 (rs11615), XRCC1 (rs25487), XRCC3 (rs861539), XPD (rs1799793, rs13181), GSTP1 (rs1695), GSTT1/GSTM1 (deletion +/-), ABCC1 (rs2074087), and ABCC2 (rs3740066, rs1885301, rs4148386).

Predictive factors for 6 12 cycles of Folfiri-Bevacizumab in metastatic colorectal cancer.

Early switching to de-intensified maintenance regimen is still a matter of debate in metastatic colorectal cancer (mCRC). The MARTHA trial, a S.I.

Genetic markers for toxicity of adjuvant oxaliplatin and fluoropyrimidines in the phase III TOSCA trial in high-risk colon cancer patients.

We investigated 17 polymorphisms in 11 genes (TS, MTHFR, ERCC1, XRCC1, XRCC3, XPD, GSTT1, GSTP1, GSTM1, ABCC1, ABCC2) for their association with the toxicity of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a prospective randomized trial of adjuvant chemotherapy. The TOSCA Italian adjuvant trial was conducted in high-risk stage II-III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In the concomitant ancillary pharmacogenetic study, the primary endpoint was the association of polymorphisms with grade 3-4 CTCAE toxicity events (grade 2-4 for neurotoxicity).

ERCC1 polymorphisms as prognostic markers in T4 breast cancer patients treated with platinum-based chemotherapy.

Background: Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1) gene have been involved in the prognosis of various cancers. In the present study, we evaluated the prognostic role of the two most common ERCC1 polymorphisms in patients with T4 breast cancer receiving platinum-based chemotherapy.

Methods: A total of 47 patients with T4 breast cancer undergoing treatment with a platinum-based regimen were collected and followed up (median 159 months; range, 42-239 months).

Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma.

Background: The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized 2x2 factorial design trial.

Methods: A total of 260 patients were randomly assigned to one of four treatment groups: (A) fotemustine and dacarbazine repeated on 3-week cycle; (B) same treatment as (A) plus IFN-α2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-α2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs.

Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia.

Background: Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia.

Methods: From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island.

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 alterations in key-regulator genes among patients with T4 breast carcinoma.

Background: Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period.

Methods: A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months.

Inflammatory breast cancer in Italy: epidemiological and clinical aspects.

Breast cancer represents the most common cancer among women in Italy. In the last decade, an increase in incidence and a decrease in mortality from breast cancer have been observed in Italy. These findings may be explained at least in part by the implementation of organized screening programs (SMPs).

Attitude of Italian medical oncologists toward palliative care for patients with advanced cancer: results of the SIO project.

Purpose: The aim of this survey was to describe the attitude of Italian oncologists towards palliative care.

Methods: A survey on palliative care was carried out among 400 Italian oncologists.

Results: Seventy-two percent indicated that the management of patients with advanced stage cancer represents the majority of their practice.

Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study.

Purpose: Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).

Long-term maintenance of prognostic value of survivin and its relationship with p53 in T4 breast cancer patients.

A large proportion of human tumors show deregulated expression of a variety of proteins that play a crucial role in the execution of the apoptotic program. Survivin belongs to the family of inhibitor of apoptosis proteins which were originally identified in baculoviruses. Ectopic expression of survivin conveys resistance to apoptosis to a variety of stimuli, and survivin is one of the most abundantly overexpressed genes in human tumors such as breast cancer.

Long-term outcomes in stage IIIB breast cancer patients who achieved less than a pathological complete response (

Purpose: Pathological complete response (pCR) to primary chemotherapy is the main determinant for improved disease-free survival (DFS) and overall survival (OS). The primary endpoints of our study were the long-term DFS and OS rates in homogeneously treated stage IIIB breast cancer patients who failed to achieve a pCR ( View Article and Find Full Text PDF

Targeting insulin-like growth factor type 1 receptor in cancer therapy.

It is believed that the insulin-like growth factor receptor type 1 (IGF-1R) signaling pathway plays a pivotal role in cancer growth, progression, and resistance to anticancer therapies. Strategies are being developed to block IGF-1R as an anticancer treatment. We reviewed several potential strategies for disrupting the IGF axis.

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.

Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC.

Background: Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor.

Methods: Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m(2), on days 1 and 5], epirubicin [30 mg/m(2), days 1 and 5], L-leucovorin [100 mg/m(2), days 1-4], and 5-fluorouracil [300 mg/m(2), days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined.

Dose-dense primary chemotherapy, as part of multidisciplinary treatment, for inoperable stage III B breast cancer--long-term results of a phase II trial.

Background: Primary chemotherapy as part of multidisciplinary approach is the established treatment for inoperable stage III B breast cancer. The primary endpoints were conversion to operable disease and feasibility of conservative surgery (breast-conserving therapy: BCT); secondary were clinical and pathological complete response rate, local and distant control and safety of the primary regimen.

Methods: Between 1998 and 2001, 40 inoperable breast cancer patients < or =60 years, 72% T4abc and 28% T4d, received 6 cycles of primary PEV dose-dense regimen: cisplatin 50 mg/m2, epirubicin 100 mg/m2 and vinorelbine 25 mg/m2, i.

Feasibility of sequential therapy with FOLFIRI followed by docetaxel/cisplatin in patients with radically resected gastric adenocarcinoma. A randomized phase III trial.

Objective: Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting.

Methods: 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B).

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

Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site : results of an Italian multicenter, randomized, phase II study.

Background: : To date, the standard treatment for patients who have carcinoma of unknown primary site has not been established.

Methods: : In this randomized Phase II study, 66 previously untreated patients (33 patients per arm) with carcinomas of unknown primary site received cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) with either paclitaxel (70 mg/m2) or vinorelbine (25 mg/m2), and all drugs were administered intravenously on Days 1 and 8 of a 21-day cycle. Twenty-nine patients (44%) presented with > or =2 involved sites.

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.

Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study.

Background: Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer.