Elena Beretta

Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma.

The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first‐line treatment in metastatic colorectal carcinoma (CRC).

Pathological features as predictors of recurrence after radical resection of gastric cancer

The aim of this study was to investigate the pattern and timing of recurrence and to determine associated risk factors after radical resection of gastric cancer including D2 dissection.

Efficacy of Treatment with Irinotecan and Oxaliplatin Combination in FU-Resistant Metastatic Colorectal Cancer Patients

Objectives: As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer. Methods: FU resistance was defined as disease progression during or within 6 months of discontinuing first-line or adjuvant FU/leucovorin chemotherapy. The study treatment consisted of irinotecan 150 mg/m2 on days 1 and 8 followed by oxaliplatin 85 mg/m2 on day 1 every 3 weeks. In order to improve the safety profile, we changed the schedule during the study to irinotecan 300 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2 every 3 weeks. Results: Of 54 patients treated, the 45 patients with measurable disease were assessed in the efficacy analysis, whereas all patients receiving at least one cycle were evaluated in the safety analysis. Of the patients assessed for efficacy analysis, 19 cases received the first schedule and 26 patients received the second schedule. Twenty-two patients (49%) responded, 10 of the first schedule and 12 of the second schedule group. Stable disease was observed in 35% of all patients. The median response duration was 6.5 months (range 3–10), the median time to progression was 8 months (range 6–10), and the overall survival was 15 months (10–26+). The NCI-CTC grade 3 side effects documented in all of the treated patients were: nausea/vomiting (11%), diarrhea (18%), and neutropenia (7%); grade 4 diarrhea was observed in 2% of patients. Conclusion: The combination of irinotecan followed by oxaliplatin combination is well tolerated and highly active in FU-resistant metastatic colorectal cancer patients.

Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition.

Aims and Background Irinotecan (CPT-11) has been tested as a single agent in several studies, and response rates of 18-23% have been reported in first-line gastric cancer therapy. In the present study we report the safety and efficacy results combining CPT-11 with 5-fluorouracil (5-FU) and folinic acid (FA). Patients and Methods Thirty consecutive patients with metastatic gastric cancer, considered in poor clinical condition, were treated with CPT-11 and 5-FU/FA according to the FOLFIRI regimen. All enrolled cases were evaluable for toxicity and drug activity. Results The main grade 3-4 toxicity (according to the NCI-CTC criteria) was neutropenia (16%, grade 4 in 1 patient); nonhematological grade 3 toxicity consisted mainly in vomiting and diarrhea reported in 1 patient. No treatment-related serious adverse events were observed. Response was obtained in 12 patients (40%), stable disease in 2 patients (7%), while progression was documented in 16 patients (53%). Conclusions These results are very promising, and suggest that the combination of CPT-11 plus 5-FU/FA is active and well tolerated and can be considered as useful treatment in patients with metastatic gastric cancer in poor clinical condition.

Capecitabine Chemoradiation for Rectal Cancer after Curative Surgery

Abstract This study reports the tolerability and feasibility of capecitabine, an oral fluoropyrimidine, chemoradiation as postoperative treatment. Stage II-III rectal cancer patients received 2 cycles of bolus 5-FU (425 mg/m2) and leucovorin (LV) (20 mg/m2) on days 1-5 q3w followed by oral capecitabine (800 mg/m2 bid) continuously during pelvic radiotherapy (total 50.4 Gy). Two additional cycles of 5-FU/LV were finally administered. Forty-one radically resected patients (median age: 61 years) were enrolled. All patients were evaluable for safety. Grade 3 adverse events included: proctitis (n = 3, 7%), diarrhea (n = 5, 12%), and leukopenia (n = 1, 2%). The overall rate of grade 3 diarrhea and leukopenia was 15% (95% confidence interval, 5-29%). Capecitabine chemoradiation in the adjuvant setting is well tolerated and is convenient to administer. These results support the use and further study of capecitabine chemoradiation in radically resected rectal cancer patients.

Capecitabine: Indications and future perspectives in the treatment of metastatic colorectal and breast cancer

Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer.

Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer.

Aims and background As raltitrexed and oxaliplatin (L-OHP) are both effective in the treatment of colorectal cancer but have different mechanisms of action, we studied the antitumoral activity and safety of their combined use in patients with advanced colorectal cancer. Methods A 15-min intravenous infusion of raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were administered on day 1 every three weeks for a maximum of six cycles. Results The study involved 51 patients (27 males and 24 females) with a median age of 65 years (range, 43-78); 28 were aged ≥65 years. The primary tumor site was the colon in 35 patients and the rectum in 16. Thirty-four patients had received prior chemotherapy: 20 as adjuvant treatment and 14 as pretreatment. The most frequent metastatic sites were liver (18 cases), lung (10 cases), liver + lung (8 cases) and lymph nodes (3 cases). Twenty-four patients completed the entire treatment plan. The most common toxicities were transaminitis (16 patients, grade 3-4), diarrhea (six patients, grade 3), nausea/vomiting (one patient, grade 4), and asthenia (one patient, grade 3). The treatment was stopped in one patient because of prolonged grade 4 transaminitis. The adverse event profile was similar in the patients aged >65 years and <65 years. Complete responses were observed in 2 patients, partial responses in 12, stable disease in 23, and progression in 8. Conclusions The results of the study suggest that the raltitrexed plus oxaliplatin regimen is feasible and clinically active in advanced colorectal cancer.

Ovarian ablation for premenopausal early-stage breast cancer: an update.

Ovarian ablation is the oldest form of systemic treatment of breast cancer and consists of removal of the main source of estrogen biosynthesis in premenopausal women. Over the last century several different means of stopping ovarian function have been studied: surgical oophorectomy, ovarian irradiation, and more recently, chemical castration by gonadotropin-releasing hormone analog therapy. In unselected patients the response rate to ovarian ablation is of about 35% but the likelihood of response is considerably higher for patients with hormonal receptor-positive tumors, the therapy being most effective in women who are actively menstruating. In spite of this evidence, the role of ovarian ablation in the management of early-stage breast cancer still remains controversial. Here we review current evidence supporting the value of this ablative procedure as an adjuvant and update ongoing clinical research to refine our knowledge about its use.