Prognostic role of chemotherapy-induced neutropenia in first-line treatment of advanced ovarian cancer. A pooled analysis of MITO2 and MITO7 trials.

BACKGROUND: Chemotherapy-induced neutropenia (CIN) has been associated with improved prognosis in several cancer conditions. Contrasting data have been produced in ovarian cancer.

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.

TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer.

BACKGROUND: FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. METHODS: This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, L-leucovorin 200 mg/m2, 5-fluoruracil 2400 mg/m2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. DISCUSSION: The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. CLINICAL TRIAL INFORMATION: NCT03231722.

Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer.

INTRODUCTION: Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. PATIENTS AND METHODS: Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. RESULTS: Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p < .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09-7.53; p < .0001). CONCLUSION: Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti-EGFRs. IMPLICATIONS FOR PRACTICE: Right- and left-sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer. The results demonstrated the lack of activity of anti-EGFRs in RAS and BRAF wild-type, right-sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices.

Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope.

BACKGROUND: No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in "frail" elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. MATERIALS AND METHODS: Forty elderly patients (aged ≥ 75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. RESULTS: The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9-8 months) and 14.3 months (95% CI: 10.9-17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. CONCLUSION: Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. IMPLICATIONS FOR PRACTICE: Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could help select an elderly and unfit population that could benefit from anti-epidermal growth factor receptor single agent therapy. In the present study, single-agent off-label panitumumab was effective and well-tolerated as first-line treatment in frail elderly patients deemed unfit for chemotherapy for metastatic RAS and BRAF wild-type colorectal cancer.

Trans-Arterial Chemoembolization with Irinotecan-Loaded Drug-Eluting Beads (DEBIRI) and Capecitabine in Refractory Liver Prevalent Colorectal Metastases: A Phase II Single-Center Study.

PURPOSE: The purpose of this study was to evaluate feasibility, safety, tolerance, and efficacy of drug-eluting beads loaded with irinotecan (DEBIRI) in combination with capecitabine in the treatment of mCRC refractory to chemotherapy in patients affected by liver predominant metastatic disease. MATERIALS AND METHODS: Twenty patients affected by CRC hepatic metastasis with liver-dominant disease, who had progression after two or more lines of chemotherapy, were enrolled. TACE with 100 mg of Irinotecan loaded into 2-ml of 70-150 µm drug-eluting beads was administrated every 4 weeks in patients with unilobar disease (2 treatments) and every 2 weeks in patients with bilobar disease (4 treatments). All patients assumed capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks, until disease progression. Primary endpoints were safety, tolerance and overall disease control (ODC); secondary endpoints were progression free survival (PFS) and overall survival (OS). RESULTS: A total of 54 treatments were performed (54/66, 82%). No intra/peri-procedural death occurred. During the mean follow-up of 11 months, two partial responses (PR) were reported with ODC of 60% (2 PR + 10 stable disease). PFS and OS were 4 and 7.3 months, respectively. Univariate analysis showed that patients presenting with KRAS wild-type, good ECOG performance status and unilobar disease had a better prognosis. Only performance status (ECOG) correlated with OS in multivariate analysis (p = 0.03). CONCLUSION: DEBIRI with capecitabine seem to be a safe, technically feasible and well-tolerated treatment in chemotherapy refractory liver prevalent colorectal metastases.

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

BACKGROUND: Two 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 PRESENTATION: A 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. CONCLUSIONS: Anastrozole-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.