Ettore D'Argento

Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases

We have previously reported that neoadjuvant therapy with modified FOLFIRI enabled nearly a third of patients with metastatic colorectal cancer (mCRC) to undergo surgical resection of liver metastases. Here, we present data from the long-term follow-up of these patients. Forty patients received modified FOLFIRI: irinotecan 180 mg m−2, day 1; folinic acid, 200 mg m−2; and 5-fluorouracil: as a 400 mg m−2 bolus, days 1 and 2, and a 48-h continuous infusion 1200 mg m−2, from day 1. Treatment was repeated every 2 weeks, with response assessed every six cycles. Resected patients received six further cycles of chemotherapy postoperatively. Nineteen (47.5%) of 40 patients achieved an objective response; 13 (33%) underwent resection. After a median follow-up of 56 months, median survival for all patients was 31.5 months: for non-resected patients, median survival was 24 months and was not reached for resected patients. Median time to progression was 14.3 and 5.2 months for all and non-resected patients, respectively. Median disease-free (DF) survival in resected patients was 52.5 months. At 2 years, all patients were alive (8 DF), and at last follow-up, eight were alive (6 DF). Surgical resection of liver metastases after neoadjuvant treatment with modified FOLFIRI in CRC patients achieved favourable survival times.

Docetaxel and oxaliplatin combination in second-line treatment of patients with advanced gastric cancer

BackgroundIn advanced gastric cancer few data are available on the efficacy or safety of new drug combination regimens after progression following first-line chemotherapy.MethodsPatients with histologically confirmed advanced gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than 2, progressing after first-line chemotherapy, were eligible. Patients were treated with docetaxel 75 mg/m2 on day 1 and oxaliplatin 80 mg/m2 on day 2, every 3 weeks, until progression or unacceptable toxicity.ResultsBetween May 2002 and April 2005, 38 patients were enrolled. Men accounted for 73.7% of the patients and the median age was 59 years. The primary tumor was not resected in 47.4% of the patients; the peritoneum was the most frequent metastatic site (60.5%). The first-line treatment was cisplatin, epirubicin, and infusional 5-fluorouracil (ECF) in 81.5% of the patients and cisplatin and infusional 5-fluorouracil (CF) in 15.7%. The median number of cycles was 4.3. The treatment was well tolerated, with no toxic deaths. National Cancer Institute (NCI) grade III-IV neutropenia was frequent (26.3%), but no febrile neutropenia was reported. Severe asthenia (15.7%) and severe nausea (15.7%) required dose reductions in 2 patients and treatment discontinuation in another. The overall response rate was 10.5%, and 18 patients (47.3%) experienced disease stabilization (7 of them with significant clinical benefit). Median time to progression was 4.0 months (range, 2–8 months) and median overall survival was 8.1 months (range, 3–26 months). Thirteen patients (34.2%) also received third-line chemotherapy, with an irinotecan-containing regimen, and their median overall survival was higher than that of the other patients (16.3 vs 6.0 months)ConclusionThe combination of oxaliplatin and docetaxel shows only marginal activity as second-line treatment, but it has a good tolerability profile. This suggests that there is room for optimizing the schedule as well as for planning sequential treatments in gastric cancer.

Anastrozole-related acute hepatitis with autoimmune features: a case report.

BackgroundTwo cases of acute hepatitis occurring during treatment with anastrozole have previously been reported, but the underlying mechanisms of liver injury are still uncertain. We report the case of anastrozole-related acute hepatitis with some autoimmune features.Case presentationA 70-year-old woman developed acute hepatitis associated with serum antinuclear antibodies during anastrozole treatment; after drug withdrawal, liver function parameters rapidly improved and serum auto-antibodies were no longer detectable.ConclusionsAnastrozole-induced hepatotoxicity is a very rare event. Drug-drug interactions or metabolically-mediated damage might be involved, with a possible role of individual susceptibility. Our report suggests that an immune-mediated mechanism may also be considered in anastrozole-related liver injury.

ERCC1 expression affects outcome in metastatic pancreatic carcinoma treated with FOLFIRINOX: A single institution analysis

Introduction No clinically useful predictive factor has been yet identified for treatment of metastatic pancreatic cancer (mPC). It is noteworthy that FOLFIRINOX, despite its high toxicity, is effective only in some patients. We retrospectively analyzed expression of excision repair cross-complementing group-1 (ERCC1) - involved in the repair of platinum induced damage - in patients affected by mPC treated with FOLFIRINOX in order to evaluate its predictive role. Results FOLFIRINOX resulted more effective in patients with normal ERCC1 levels than in those with ERCC1 hyper-expression. Median progression free survival (PFS) was 11 vs. 4 months (HR 0.26; 95% CI 0.14-0.50; p<.0001), median overall survival (OS) 16 vs. 8 months (HR 0.23; 95% CI 0.12-0.46; p<.0001) and disease control rate (DCR) 93% vs. 50% (p=0.00006). The advantage was confirmed at univariate and multivariate analysis. Patients and Methods 71 patients with histologically proven mPC and treated with FOLFIRINOX as first-line therapy were considered eligible. mRNA ERCC1 expression was determined using RT-PCR analysis. Discussion ERCC1 might be an effective predictor of response to FOLFIRINOX in mPC. Patients overexpressing ERCC1 should be excluded by this often toxic therapy and referred to an alternative treatment.

Maintenance hormonal and chemotherapy treatment in metastatic breast cancer: a systematic review.

Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine therapy and in hormone-negative disease. Optimal duration, efficacy and safety of a maintenance endocrine therapy or chemotherapy after an induction treatment are still a matter of debate. We performed a literature review to identify studies regarding maintenance hormonal and chemotherapy treatments in metastatic breast cancer. We analyzed data relating to efficacy (improvement of progression-free survival and overall survival) and safety (symptoms relief and quality of life [QoL]). Maintenance endocrine therapy could prolong progression-free survival with a better control of symptoms and improving QoL. Maintenance chemotherapy prolong the response to a previous treatment, worsening the QoL, except for metronomic capecitabine.

The interference between oxaliplatin & anti-EGFR therapies: a different hypothesis to explain the ‘unexplainable’

This paper has been written because we have a differing idea concerning the suspected negative interference between oxaliplatin and anti-EGFR therapies in cancer patients. Several multicenter, randomized, controlled clinical trials investigated whether the efficacy of oxaliplatin-based chemotherapy is improved by the addition of anti-EGFR therapies in patients affected by KRAS wild-type advanced colorectal cancer. Results of these trials have produced puzzling findings, with some studies demonstrating improved survival and other studies showing no differences in overall survival between experimental and control arms. Moreover, a detrimental effect has been demonstrated in some settings. Nevertheless, the extent of this interaction remains uncertain. Some physicians proposed personal interpretations. This paper describes our hypothesis.

DEBIRI plus capecitabine: a treatment option for refractory liver-dominant metastases from colorectal cancer

AIM This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases. PATIENTS & METHODS Forty patients with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m2 twice daily on days 1-14 every 3 weeks. RESULTS Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients. CONCLUSION DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.

Gastrointestinal stromal tumors (GISTs) and second malignancies A novel sentinel tumor? A monoinstitutional, STROBE-compliant observational analysis

AbstractSeveral evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis.A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-&agr; genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms.Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-&agr; mutation (n. 2) and exon 18 PDGFR-&agr; mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months.The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis.