Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations

Abstract

BackgroundPharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).Patients and methods.Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.ResultsFifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2–3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.ConclusionsWhile patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.

Combination of icotinib and chemotherapy as first-line treatment for advanced lung adenocarcinoma in patients with sensitive EGFR mutations: A randomized controlled study

“…In vitro studies showed that pretreatment with erlotinib caused arrest of cells in G1 phase, decreasing the cytotoxicity of chemotherapy and reducing apoptosis, which would negatively affect the efficacy of chemotherapy [17]. One the other hand, it was discovered that temporary discontinuance of TKIs before chemotherapy allows the cancer cells to re-enter the cell cycle, restoring their sensitivity to chemotherapy [18][19][20]. The strategy was also supported by FASTACT-2 and several other clinical researches [21][22][23].…”

Fibulin-3 as a biomarker of response to treatment in malignant mesothelioma

“… 28 Sporadically a NMR was done to evaluate the operability of some patients 29 and a PET-CT was also done in some patients to evaluate the extent of disease and response to treatment like in patients with lung cancer. 30 …”

Outcome of severe infections in afebrile neutropenic cancer patients

“…Neutropenia is a major risk factor for the development of infection in cancer patients undergoing treatment with chemotherapy. 2,3 Fever remains the most prevalent and evident sign of infection in neutropenic cancer patients and early initiation of broad-spectrum antibiotic therapy significantly reduces mortality in these patients. 4–7 …”