[show abstract][hide abstract] ABSTRACT: Oxaliplatin (OXA), raltitrexed (RTX), 5-fluorouracil (FU) and folinic acid (FA) have shown activity in metastatic colorectal cancer, radioenhancing effect and synergism when combined. We evaluated a chemotherapy (CT) combination of OXA, RTX and FU/FA during preoperative radiotherapy (RT) in locally advanced rectal cancer (LARC) patients. Fifty-one patients with LARC at high risk of recurrence (T4, N+ or T3N0 < or =5 cm from anal verge and/or circumferential resection margin < or =5 mm) received three biweekly courses of CT during pelvic RT (45 Gy). Surgery was planned 8 weeks after CT-RT. Recommended doses (RDs) determined during phase I were utilised in the subsequent phase II trial, where the rate of tumour regression grade (TRG) 1 or 2 was the main end point. No toxic deaths occurred, and severe toxicity was easily managed. In phase II, RDs delivered in 31 patients were OXA 100 mg m(-2) and RTX 2.5 mg m(-2) on day 1, and FU 900 mg m(-2) and LFA 250 mg m(-2) on day 2. Main severe toxicities by patients were grade 4 neutropenia (23%) and grade 3 diarrhoea (19%). In 71% (95% confidence limits, 52-86%) of patients, TRG1 (13) or TRG2 (9) was obtained. All patients are alive and recurrence-free after a median follow-up of 29 months. Combination of OXA, RTX and FU/FA with pelvic RT has an acceptable toxicity and a high clinical activity in LARC and should be studied further in patients at high risk of recurrence.
British Journal of Cancer 06/2006; 94(12):1809-15. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients; CMF (cyclophosphamide, methotrexate, fluorouracil) can be reasonably considered the most widely accepted standard of treatment.
We retrospectively reviewed compliance and safety of adjuvant CMF in patients older than 60. The treatment was indicated if patients had no severe comorbidity, a high-risk of recurrence, and were younger than 75. Toxicity was coded by NCI-CTC. Toxicity and compliance were compared between two age subgroups (< 65, > or = 65) by Fisher exact test and exact Wilcoxon rank-sum test.
From March 1991 to March 2002, 180 patients were identified, 100 older than 60 and younger than 65, and 80 aged 65 or older. Febrile neutropenia was more frequent among older patients (p = 0.05). Leukopenia, neutropenia, nausea, cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies, while mucositis tended to be more evident among younger patients, all not significantly. Almost one half (47%) of the older patients receiving concomitant radiotherapy experienced grade 3-4 haematological toxicity. Compliance was similar in the two groups, with 6 cycles administered in 86% and 79%, day-8 chemotherapy omitted at least once in 36% and 39%, dose reduction in 27% and 38%, prolonged treatment duration (> or = 29 weeks) in 10% and 11% and need of G-CSF in 9% and 18%, among younger and older patients, respectively.
Our data show that, in a highly selected population of patients 65 or more years old, CMF is as feasible as in patients older than 60 and younger than 65, but with a relevant burden of toxicity. We suggest that prospective trials in elderly patients testing less toxic treatment schemes are mandatory before indicating adjuvant chemotherapy to all elderly patients with significant risk of breast cancer recurrence.
[show abstract][hide abstract] ABSTRACT: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value.
CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases.
Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively.
These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.
Clinical Cancer Research 05/2004; 10(8):2824-31. · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Preoperative chemoradiation allows downstaging of locally advanced rectal cancer and in selected patients also a sufficient downsizing to ensure sphincter preservation. Selection of patients warranting a preoperative approach is improved by magnetic resonance imaging (MRI) which is able to define the involvement of mesorectal circumferential margin. Similarly it would be crucial to define the response to chemoradiation during the treatment but traditional morphologic imaging techniques may fail in differentiating neoplastic tissue from scarring. PET-FDG has been successfully used in the detection of metastatic colorectal cancer allowing imaging of deposits as small as 0.5 cm and may have a role in evaluating early response to chemoradiation.
In the present study, in patients with T3-T4 rectal cancer undergoing preoperative chemoradiation PET-FDG and flow cytometry analysis on endoscopic biopsy specimen have been performed before, during and after preoperative chemoradiation.
Chemoradiation treatment has been successful in terms of downsizing and downstaging of the tumor. PET-FDG was able to demonstrate local response at only ten-fifteen days after the beginning of neoadjuvant therapy, also identifying non responding patients.
FDG-PET may have a role in defining the response to chemoradiation and modulate the treatments strategy in patients with advanced rectal cancer.