Timmer-Bonte, J.N., Punt, C.J., vd Heijden, H.F., van Die, C.E., Bussink, J., Beijnen, J.H., . . . Tjan-Heijnen, V.C. (2008). Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer. Lung Cancer, 60, 222–230.
The purpose of the study was to establish the maximum-tolerated dose of paclitaxel and investigate whether prophylactic G-CSF and antibiotics would allow further dose escalation of paclitaxel in treatment-naïve patients.
Doses were given in increasing increments to groups of three patients to determine dose-limiting toxicity (DLT). Part A: Paclitaxel escalation without prophylactic G-CSF (unless DLT from neuropathy). Part B: Level 7 etoposide administered with G-CSF. Part C: Same as part B plus prophylactic antibiotics (ciprofloxacin and roxithromycin). With a hematologic toxicity recovery to CTC less than 3, a subsequent cycle was allowable with a max delay of two weeks. Dose reduction was given if grade 2 CTC hematologic toxicity persisted after a two-week delay and/or there was a greater than grade 2 nephro- or neurotoxicity.
Single-site outpatient setting in the Netherlands.
Active treatment
Prospective dose-finding study.
In total, 189 cycles of chemotherapy were administered. Forty-three of the 47 patients enrolled survived treatments. Thirty-four completed the full protocol (febrile neutropenia or dose delays from toxicity were the main reasons for incomplete cycles).
The use of G-CSF and antibiotics allows for higher chemotherapy doses in patients with stage IIIA, IIIB, and IV non-small cell lung cancer, which could increases survival.
The administration of G-CSF and prophylactic antibiotics may reduce neutropenia and infections increasing the DLT, allowing for higher doses of chemotherapy for better chance of prolonged survival. However, research in this area needs further exploration.