ABSTRACT
PURPOSE: Paclitaxel and docetaxel are two taxanes approved for the treatment of non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding the efficacy of docetaxel in NSCLC previously treated with a paclitaxel-platinum doublet (PP). The aim of our study was to evaluate the response to docetaxel in NSCLC patients with prior PP treatment. METHODS: Patients with stage IV NSCLC treated with PP that presented disease progression and received docetaxel as second-line treatment were included. Demographics, clinical characteristics, EGFR mutation status, objective response (OR), overall survival (OS), progression-free survival (PFS), and PFS without chemotherapy after first line with PP were analyzed. RESULTS: Sixty-three patients were evaluated. Median age was 58 years, 54% of patients were women, 53% were never-smokers, and 39% had EGFR mutations. OR and median PFS for PP were 36.5% and 6.7 months, respectively. OR and median PFS for docetaxel were 19% and 3.8 months, respectively. Patients with EGFR mutations had better response to docetaxel compared with wild-type patients (26 vs. 17%, p = 0.028). However, only long PFS (>6 months) to first-line PP was independently associated with a higher OR [RR 6.3, 95% CI (1.03-38.4), p = 0.046], and longer PFS [0.49 (0.25-0.9)] and OS [0.2 (0.06-0.7), p = 0.008] to second-line docetaxel compared with patients with short PFS (≤6 months) to PP. CONCLUSIONS: Previous use of PP does not preclude a favorable response to docetaxel in NSCLC. Long PFS with PP may help select NSCLC patients who benefit from second-line docetaxel.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Paclitaxel , Taxoids , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/physiopathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Disease Progression , Disease-Free Survival , Docetaxel , Drug Screening Assays, Antitumor , Female , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Mexico/epidemiology , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Patient Selection , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: There are currently no available biomarkers for advanced pleural mesothelioma that determine which patients could benefit from a specific chemotherapy regimen. METHODS: Based on the results of a previously published phase II study, we associated the (99m)Technetium-labelled liposomal doxorubicin ((99m)Tc-LD) uptake value (75 % cut-off) with the response rate, progression-free survival and overall survival of patients treated with a combination of liposomal doxorubicin and cisplatin. RESULTS: Patients with tumours exhibiting increased (99m)Tc-LD uptake showed better response rates, progression-free survival and overall survival than those exhibiting lower uptake 73.3 versus 15 % (p < 0.001); 6.9 versus 3.2 months (p = 0.033) and 23 versus 6.6 months (p = 0.001), respectively. CONCLUSION: (99m)Tc-DL uptake in tumour tissue could define a set of patients who would benefit from this chemotherapy regimen.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Cisplatin/therapeutic use , Doxorubicin/pharmacokinetics , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Radiopharmaceuticals , Technetium , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/metabolism , Doxorubicin/therapeutic use , Female , Follow-Up Studies , Humans , Liposomes , Male , Mesothelioma/diagnosis , Mesothelioma/pathology , Middle Aged , Neoplasm Staging , Pharmaceutical Vehicles , Pleural Neoplasms/diagnosis , Pleural Neoplasms/pathology , Prognosis , Survival Analysis , Tissue Distribution , Tumor Burden/drug effectsABSTRACT
PURPOSE: Low-dose, prolonged infusion of gemcitabine has effects similar to standard doses in several cancers. We evaluated the toxicity and efficacy of low-dose gemcitabine in prolonged infusion plus cisplatin in patients with advanced pleural mesothelioma. METHODS: Patients with mesothelioma received gemcitabine (250 mg/m(2)) in a 6-h infusion plus cisplatin (35 mg/m(2)) on days 1 and 8 every three weeks. We used the modified response evaluation criteria in solid tumours. This study is registered in clinical trials (NCT01869023). RESULTS: We included 39 patients; 82.1 % were low risk according to the European Organisation for Research and Treatment of Cancer prognostic group. Partial response was observed in 53.8 % (21/39), stable disease in 33.3 % (13/39) and progression in 12.8 % (5/39). The median progression-free survival was 6.9 months (95 % CI 3.2-10.6 months), and the associated factors were the EORTC risk and histology. The median overall survival was 20.7 months (95 % CI 10.7-30.8 months). The functional, physical and emotional roles and dyspnoea, insomnia and pain symptom scales improved. The most commonly graded 3/4 side effects were neutropenia (24.4 %), lymphopenia (14.6 %), thrombocytopenia (14.7 %) and anaemia (12.2 %). CONCLUSIONS: Low-dose, prolonged gemcitabine infusion plus cisplatin has acceptable toxicity and high efficacy with improved quality of life, representing an affordable regimen for the low-income population.
