The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC.
Overall, 95 patients received pemetrexed 500 mg/m2 i.v. over Day 1 of a 21-day cycle. ...Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria.
Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression.
Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.
Abstract
Background
Preop CTRT is the standard of treatment of LARC and it results in significant tumor downstaging and local control with a complete pathological response (pCR) rate of about 15%. ...Immunotherapy can lead up to a 50% of response in metastatic colorectal cancer (mCRC) with deficient mismatch repair (MMR) status, but its activity is extremely low in MMR proficient mCRC. In this context, the role of RT in revert the tolerance to a low neoantigen-burden by the induction of antigen release from the tumour and activation of dendritic cells leading to a CD8+ T lymphocyte-mediated anticancer immune response has been widely elucidated. Furthermore, in LARC pts, preop CTRT increases PD-L1 expression in tumor cells, strongly suggesting a neoadjuvant combinatory strategy with RT and PD-1/PD-L1 pathway blockade. On the basis of such premises we are conducting the AVANA study to explore the role of Ave in combination with preop CTRT in LARC.
Trial design
This is an Italian multi-center, phase II study. Pts with resectable LARC, defined by the presence of at least one of the following features, cN+, cT4, high risk cT3, receive standard preop CTRT (external-beam RT 50.4 Gray in 28 fractions over 5.5 weeks + capecitabine 825 mg/sqm/bid 5 days/week) plus 6 cycles of Ave 10 mg/Kg every 2 weeks. Surgery with total mesorectal excision is performed at week 8-10 after the end of CTRT. Postop CT is recommended according to pathologic response. The primary end-point is pCR rate. Secondary end-points are R0 resection rate, tumor downstaging, local recurrence, sphincter preservation rate, progression-free survival, overall survival, safety profile and the evaluation of exploratory predictive and/or prognostic biomarkers. Assuming as null hypothesis p0 a pCR rate of 15%, a significance level of 5% (one-sided) and a power of 80%, a sample size of 101 pts is needed to detect an absolute increment of 10% in pCR rate (from 15% to 25%). The experimental regimen will be considered for further studies if in at least 22 pts we observe a pCR. The enrollment is ongoing. Sponsored by GONO and partially supported by Merck.
Clinical trial identification
2017-003582-10.
Legal entity responsible for the study
GONO.
Funding
Merck KGaA.
Disclosure
All authors have declared no conflicts of interest.
This study was designed to evaluate the efficacy and safety of irinotecan/cetuximab administered as third- or fourth-line therapy in a retrospective series of patients with metastatic colorectal ...cancer refractory to oxaliplatin and irinotecan.
Most patients (90%) had been previously treated with adjuvant 5-fluorouracil/leucovorin, and all had received oxaliplatin-based regimens before receiving irinotecanbased second-line treatment. Sixty patients with irinotecan-refractory colorectal cancer received a regimen comprising weekly irinotecan 120 mg/m
2 as a 1-hour intravenous infusion and cetuximab 400 mg/m
2 infused over 2 hours as the initial dose and 250 mg/m
2 infused over 1 hour for the subsequent administrations. A single treatment cycle comprised 4 weekly infusions followed by 2 weeks of rest.
According to an intent-totreat analysis, a partial response was exhibited in 12 of 60 enrolled patients (20%; 95% confidence interval, 11%-32%) with a median duration of 5.1 months (range, 3–7.4 months). The tumor growth control rate was 50% (95% confidence interval, 37%-63%). Objective responses did not correlate with performance status, number of sites of disease, and pretreatments or epidermal growth factor receptor status. The median progression-free survival was 3.1 months (range, 1.2–9 months), whereas median overall survival was 6 months (range, 2–13 months). Both survival parameters correlated with performance status at the beginning of treatment. The main grade 3/4 toxicities were nausea (33%), diarrhea (27%), leukopenia (18%), asthenia (13%), and acne-like reaction (13%).
Our data suggest that the weekly irinotecan/cetuximab regimen is feasible in an outpatient setting and tolerated by most patients. At present, combinations of chemotherapy with cetuximab are being evaluated in patients with earlier-stage disease in a number of ongoing studies.
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.
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). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.
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