Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study.

BACKGROUND: Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer. METHODS: Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or maximum 24 months. Primary endpoint was time-to-treatment failure (TTF) and secondary were progression-free survival (PFS), toxicity, changes in blood concentrations of angiogenesis-associated biomarkers and pharmacokinetics. RESULTS: Seventy-three patients were enrolled. Four-month TTF rate did not differ between the three arms: 25.9% (11.1%-46.2% 95% Confidence Interval), 33.3% (15.6%-55.3%) and 18.2% (5.2%-40.3%) for the 30 mg, 40 mg and 50 mg arms (p-value = 0.56). Objective response was seen in 2 patients with NSCLC (treated at 30 and 50 mg respectively), one with BC (at 40 m g) and one with PC (at 50 mg) and lasted from 4 to 100 weeks, with maximum response duration achieved at 50 mg. Adverse events were mild and negligible and did not differ between the three arms. Blood levels of vinorelbine reached steady state from the second week of treatment and mean values for the 30, 40 and 50 mg were respectively 1.8 ng/ml (SD 1.10), 2.2 ng/ml (SD 1.87) and 2.6 ng/ml (SD 0.69). Low pre-treatment blood concentrations of FGF2 and IL8 predicted favorable response to therapy (p values 0.02 and 0.006, respectively), while high levels of TEK gene transcript predicted treatment resistance. CONCLUSIONS: Considering the antitumor activity and response duration, the negligible toxicity of the highest dose investigated and the lack of drug accumulation over time, we suggest that 50 mg given three times a week is the optimal dose for metronomic oral vinorelbine. Further investigation of metronomic oral vinorelbine (MOVIN) at this dose is warranted in combination with conventional chemotherapy regimens and targeted therapies. TRIAL REGISTRATION: Clinicaltrials.gov NCT00278070.

Administration of cisplatin in three patients with carboplatin hypersensitivity: is skin testing useful?

Carboplatin is a chemotherapeutic agent approved in the first-line setting of numerous malignancies. Hypersensitivity to carboplatin has been reported in up to 44% of patients receiving this antineoplastic agent, usually occurring after several courses of treatment. The aim of this study was to determine the usefulness of skin tests in ruling out cross-reaction to cisplatin to continue platinum-based chemotherapy in patients who are responsive to these agents. Prick tests and intradermal tests with a series of dilutions of carboplatin and cisplatin were performed on three patients who had exhibited medium and severe hypersensitivity reactions to carboplatin. Prick tests were negative in both the antineoplastic agents. Intradermal tests with carboplatin were positive in all three patients and negative with cisplatin. In all patients, the administration of cisplatin instead of carboplatin was well tolerated without the need of premedication. In conclusion, intradermal skin tests can be a useful tool for detecting a potential cross-reaction between platinum salts. It allows safe administration of a different platinum agent in patients who seem to benefit from platinum-based therapy. Discontinuation of chemotherapy, desensitization protocols and steroid premedication can be avoided.

Triplet combination of carboplatin, irinotecan, and etoposide in the first-line treatment of extensive small-cell lung cancer: a single-institution phase II study.

Small-cell lung cancer is a rapidly progressive tumor and median survival is less than 10 months in patients with extensive stage of the disease. This study aims to evaluate the efficacy and tolerability of the carboplatin, etoposide, and irinotecan triplet as a first-line treatment in extensive small-cell lung cancer. Chemonaive patients with documented diagnosis of extensive small-cell lung cancer, performance status 0-2, and adequate organ function were eligible. Patients received triweekly carboplatin area under the curve 5 on day 1, irinotecan 150 mg/m on day 2, and etoposide 75 mg/m on days 1, 2, and 3 for up to six cycles. A total of 54 patients were enrolled. Forty-seven of 54 patients (87%) had a performance status of 0-1. The response rate was 75% and complete response was achieved in 10 of 54 patients (18%). The median time to progression was estimated at 8 months (95% confidence interval: 6.6-8.9) and median overall survival at 12 months (95% confidence interval: 10.3-13.9). Patients with one site of metastases had prolonged survival as compared with those with two or more sites. Normalization of lactate dehydrogenase values after treatment was not correlated to survival. Grade 3-4 neutropenia occurred in nine patients (16.7%) and grade 3 fetal thrombocytopenia in one patient (1.9%). Two toxic deaths (3.7%) were reported. The carboplatin, irinotecan, and etoposide triplet is a very effective and well-tolerated combination for the poor prognosis group of extensive-stage small-cell lung cancer patients.

Chemotherapy-induced neutropenia in lung cancer patients: the role of antibiotic prophylaxis.

Chemotherapy-induced neutropenia can cause fatal bacterial infections. Colony-stimulating factors (CSFs) are usually recommended as prophylaxis, while routine use of prophylactic antibiotics remains controversial. Based on our literature search in PubMed, quinolones and trimethoprim/sulfamethoxazole were the most frequently used prophylaxis, while CSFs were administered in 22.1% of patients. Lung cancer patients who received prophylactic antibiotics exhibited significantly fewer episodes of febrile neutropenia, fewer documented infections as well as shorter duration of related hospitalisations. Prophylactic use of wide spectrum antibiotics seems effective and should be considered as an alternative strategy in the prevention of chemotherapy-induced neutropenia in lung cancer patients.