title: First assessment of whole-brain radiation therapy combined with pemetrexed-based chemotherapy in non-small-cell lung carcinoma: data on safety and efficacy.
abstract: The folate antimetabolite pemetrexed was approved for the treatment of patients with metastatic nonsquamous non-small-cell lung carcinoma. Its activity on brain metastases makes pemetrexed attractive in combination with whole-brain radiation therapy (WBRT), but it could also potentially increase toxicity. We examined the medical records of 43 consecutive patients with brain metastases from non-small-cell lung carcinoma. Patients received pemetrexed-based chemotherapy at a dose of 500 mg/m. The median total number of pemetrexed-based chemotherapy cycles was 4 (range: 1-28). During the course of chemotherapy, patients received WBRT delivering 30 Gy in 10 fractions (n=34) or 20 Gy in five fractions (n=9). The median follow-up time was 30.5 weeks (range: 1-79 weeks). Intracranial progression was a cause of death in nine patients (20.9%). Clinical benefit of WBRT was reported in 30 patients (69.8%). The best radiological response was a complete response in eight patients (18.6%), a partial response in 16 patients (37.2%), stable disease in 11 patients (25.6%), and progression in four patients (9.3%). A stable intracranial disease until the last follow-up was observed in 26 patients (60.5%). The median estimated overall survival was 31 weeks (95% CI: 24-37 weeks). Most WBRT-related toxicities were low and 21 patients (48.9%) had no reported acute neurological toxicity. One patient developed unexplained encephalopathy 5 weeks after WBRT completion in the context of progressive diffuse brain metastases. The combination of pemetrexed with WBRT led to considerable clinical improvement and tumor responses in most patients. Overall neurological toxicity was rather low. A clinical trial is essential for better analysis of the potential synergistic effects of a drug with radiation and evaluation of neurological toxicity.
authors.affiliation: Department of Medical and Radiation Therapy, Hôpital d'Instruction des Armées du Val-de-Grâce, Paris, France. chargari-vdg@hotmail.fr
authors.forename: Cyrus
authors.initials: C
authors.lastname: Chargari
authors.forename: Cécile
authors.initials: C
authors.lastname: Pacaut
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Le Moulec
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moriceau
authors.forename: Yassine
authors.initials: Y
authors.lastname: Moussaid
authors.forename: Romain
authors.initials: R
authors.lastname: Rivoirard
authors.forename: Renaud
authors.initials: R
authors.lastname: Dulou
authors.forename: Julian
authors.initials: J
authors.lastname: Jacob
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Guy
authors.forename: Olivier
authors.initials: O
authors.lastname: Bauduceau
authors.forename: Bernard
authors.initials: B
authors.lastname: Ceccaldi
authors.forename: Lionel
authors.initials: L
authors.lastname: Védrine
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine