Staging and monitoring of small cell lung cancer using [18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET).

BACKGROUND: [18F]Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is widely used for the staging evaluation of nonsmall cell lung cancer, however, its use in small cell lung cancer (SCLC) remains investigational. PATIENT AND METHODS: We designed a prospective study to evaluate the role of PET in SCLC. Patients with SCLC underwent PET scanning as well as conventional imaging before and after treatment. RESULTS: A total of 39 PET scan examinations were performed in 21 patients with SCLC; 18 studies were performed before first-line chemotherapy and 21 studies were done during or after treatment. PET findings were compared with findings on CT scans of the chest or abdomen and bone scan. Discordant findings were detected in 14 out of 383 comparisons (4%) for 10 anatomic sites. In the thorax and the abdomen, PET agreed with CT scan in 92% to 100% of examinations assessing potential disease sites, including the contralateral chest, liver, and adrenals. PET agreed with bone scan in detecting bony lesions in 27 out of 32 imaging studies (84%): in 4 out of 5 discordant cases, PET findings were true and in 1 case indeterminate. Staging at baseline (limited, n = 6; extensive, n = 12) was identical when PET and sum of other staging procedures were compared. Response assessment was concordant between PET and CT scans in 8 of 9 patients who had evaluation before and after first-line chemotherapy. CONCLUSIONS: PET is potentially useful for the initial staging and monitoring of patients with SCLC and it may be superior to bone scan in detecting bone metastasis. The cost effectiveness of PET scan in SCLC remains to be determined.

Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer.

PURPOSE: We studied the toxicities, potential pharmacokinetic interactions, and preliminary antitumor activity of the combination of docetaxel and irinotecan with celecoxib, a selective cyclooxygenase-2 inhibitor. PATIENTS AND METHODS: Eligible patients had advanced non-small lung cancer (NSCLC) with measurable disease, good performance status, and adequate end organ function. Docetaxel and irinotecan were administered intravenously on days 1 and 8, every 21 days, and their doses were escalated on successive patient cohorts at three dose levels: 30/50, 30/60, and 35/60 (doses in mg/m2). Celecoxib was administered at a starting dose of 400 mg orally twice daily without interruption, beginning on day 2 of cycle 1. Pharmacokinetic studies were performed on day 1 of cycle 1 and day 1 of cycle 2. RESULTS: Seventeen patients with advanced NSCLC were enrolled and collectively received 78 cycles of therapy. Diarrhea was the most common toxicity; it was noted in 13 patients (76%). Dose-limiting toxicities occurred at dose level 1 (myocardial infarction in a patient with multiple coronary artery disease risk factors) and dose level 3 (grade 4 neutropenia with fatal urosepsis). Other major toxicities were: grade 3 neutropenia (2 patients); grade 3/4 diarrhea (3/1); grade 3 nausea (2); grade 2 rash (1); and grade 3 pneumonitis (1). The maximum tolerated dose was at dose level 3, i.e., docetaxel 35 mg/m2 and irinotecan 60 mg/m2 on days 1 and 8, plus celecoxib 400 mg twice daily, repeated every 21 days. Five of 15 evaluable patients achieved an objective response. The pharmacokinetics of docetaxel were not altered by celecoxib. However, we observed an 18% increase in the average elimination clearance of irinotecan coincident with the addition of celecoxib. CONCLUSIONS: The addition of celecoxib to docetaxel and irinotecan was generally well tolerated but unpredictable fatal toxicity occurred. Diarrhea was the most common toxicity. Antitumor activity was promising. The alteration of irinotecan pharmacokinetic parameters observed may not be clinically relevant.

Pemetrexed: a novel antifolate agent enters clinical practice.

Pemetrexed (Alimta, Eli Lilly) is a multitargeted antifolate that inhibits at least three enzymes in the nucleic acid synthetic pathways. The US Food and Drug Administration recently approved pemetrexed, in combination with cisplatin, for the first-line treatment of advanced malignant pleural mesothelioma. Moreover, pemetrexed was recently shown to be as efficacious as docetaxel (Taxotere, Aventis) in the second-line treatment of non-small cell lung cancer, and its toxicity profile was preferable. The main toxicity seen with pemetrexed is myelosuppression, which is considerably reduced by coadministration of folic acid and vitamin B12. Multiple Phase II clinical trials have demonstrated that pemetrexed has promising single-agent activity in many other solid tumors, including head and neck, breast and colorectal cancers. Combination regimens consisting of pemetrexed and other chemotherapeutics or novel molecular-targeted agents are currently under investigation. Future studies will better define and likely expand the role of pemetrexed for the treatment of cancer.