title: Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer. A phase I/II dose escalation trial.
abstract: In this phase I/II study, we investigated the radiosensitising effects of docetaxel in non-small cell lung cancer (NSCLC). 30 patients with stage IIIb (18 patients) and IV (12 patients) NSCLC were treated with 64 Gy of accelerated chest radiotherapy (5-week schedule using a concomitant boost technique) and docetaxel on a weekly basis. The docetaxel starting dose level was 20 mg/m2/week and was escalated by 10 mg/m2 increments in cohorts of 10 patients. Dose-limiting toxicity (grade 3 asthenia) was observed in 6 of 10 patients treated at the 40 mg/m2/week dose level, enforcing a 50% dose reduction in 4 patients. Grade 3 neutropenia was observed in 5 of 30 patients (17%), 3 of which were treated at the high dose level. Peripheral neuropathy occurred in 3 (10%) patients. A significant decrease in the absolute lymphocyte count was observed in all patients; the nadir was reached on day 28 (mean +/- standard deviation (S.D.) = 539 +/- 363/ml) compared with pretreatment values (mean +/- S.D. = 1842 +/- 863/ml; P = 0.002). 6 out of 30 patients (20%) experienced grade 3 oesophagitis, resulting in a 1-2 week delay in overall treatment time. Complete response of the primary tumour was observed in 8 (27%) patients assessed 2 months after treatment. 4 of these patients had disease resistant to previous docetaxel-containing chemotherapy. A partial response occurred in 15 of 30 patients (50%) for an overall response rate of 77% (95% confidence interval (CI) 60-92%). Radiosensitisation with docetaxel is feasible and the recommended dose for further phase II studies is 30 mg/m2/week. Further phase II studies are required to confirm the remarkably high response rate observed in the present trial.
authors.affiliation: Department of Radiation Oncology, University Hospital of Heraklion, Crete, Greece.
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: C
authors.initials: C
authors.lastname: Kourousis
authors.forename: M
authors.initials: M
authors.lastname: Kamilaki
authors.forename: S
authors.initials: S
authors.lastname: Koukouraki
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.forename: N
authors.initials: N
authors.lastname: Androulakis
authors.forename: N
authors.initials: N
authors.lastname: Bahlitzanakis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011878:Radiotherapy / Q000009:adverse effects; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel