Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma.

PURPOSE: This multicenter, phase III study compared overall survival (OS) of second-line pemetrexed plus best supportive care (BSC) versus BSC alone in patients with advanced malignant pleural mesothelioma (MPM). Secondary end points included response rate, progression-free survival (PFS), time to tumor progression (TTP), time to treatment failure (TTF), and toxicity. PATIENTS AND METHODS: Patients with relapsed MPM after first-line chemotherapy were randomly assigned to receive pemetrexed 500 mg/m(2) plus BSC (P+BSC) every 21 days or BSC alone. RESULTS: The study enrolled 243 patients (123 on P+BSC arm and 120 on BSC arm). Median OS time was not significantly different between the arms (8.4 months for P+BSC and 9.7 months for BSC; P = .74). Cox regression modeling suggested a trending survival benefit for patients who responded to first-line therapy. Time-to-event measures significantly favored P+BSC (median PFS, TTP, and TTF). Partial response was achieved in 18.7% and 1.7% of patients in P+BSC and BSC arms, respectively (P < .0001), and a disease control rate (partial response plus stable disease) was achieved in 59.3% and 19.2% of patients in P+BSC and BSC arms, respectively (P < .0001). Use of postdiscontinuation chemotherapy was significantly greater among BSC patients compared with P+BSC patients (51.7% v 28.5%, respectively; P = .0002), with more BSC patients receiving pemetrexed (18.3% v 3.3%, respectively; P = .0001). Postdiscontinuation therapy was initiated earlier for BSC than P+BSC patients (median time to initiation, 4.3 v 15.7 months, respectively; log-rank P < .0001). Chemotherapy was well tolerated, with expected modest (4% to 7%) grade 3 and 4 hematologic toxicities. CONCLUSION: Second-line pemetrexed elicited significant tumor response and delayed disease progression compared with BSC alone in patients with advanced MPM. Improvement in OS was not seen in this study, possibly because of the significant imbalance in postdiscontinuation chemotherapy between the arms.

Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer (NSCLC) using four-dimensional CT scans for treatment planning.

We reviewed response rates, local control, survival and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors. Forty patients with stage I non-small cell lung cancer (NSCLC) underwent radiosurgery involving single-dose irradiation. The standard dose prescribed to the isocenter was 30Gy with an axial safety margin of 10mm and a longitudinal safety margin of 15mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed. The volume of the bronchial carcinomas varied from 4.2 to 130cm(3) (median: 19.5cm(3)), and the PTV derived from four-dimensional CT (4D-CT) scans using image fusion ranged from 15.6 to 390.5cm(3) (median: 101cm(3)). Tumor size ranged from 1.7 to 10cm at largest focuses. Follow-up periods varied from 6.0 to 61.5 months (median: 20 months). We observed three local tumor recurrences, resulting in an actuarial local tumor control of 81% at 3 years. With the exception of two rib fractures, no serious late toxicity was observed. The overall survival probability rates were: 2 years: 66%, 3 years: 53% (median overall survival: 37 months). Cancer-specific survival probability was: 2 years: 71%, 3 years: 57%. Non-fractionated high single-dose SBRT for NSCLC is more convenient for the patient and less time-consuming than hypofractionated SBRT, but data dealing with this method are still scanty. This alternative treatment results in favourable local control and acceptable toxicity.

Stereotactic, single-dose irradiation of stage I non-small cell lung cancer and lung metastases.

BACKGROUND: We prospectively reviewed response rates, local control, and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors. METHODS: Fifty-eight patients underwent radiosurgery involving single-dose irradiation. With 25 patients, 31 metastases in the lungs were irradiated; with each of 33 patients, stage I non-small cell lung cancer (NSCLC) was subject to irradiation. The standard dose prescribed to the isocenter was 30 Gy with an axial safety margin of 10 mm and a longitudinal safety margin of 15 mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed. RESULTS: The volume of the metastases (CTV) varied from 2.8 to 55.8 cm3 (median: 6.0 cm3) and the PTV varied from 12.2 to 184.0 cm3 (median: 45.0 cm3). The metastases ranged from 0.7 to 4.5 cm in largest diameter. The volume of the bronchial carcinomas varied from 4.2 to 125.4 cm3 (median: 17.5 cm3) and the PTV from 15.6 to 387.3 cm3 (median: 99.8 cm3). The bronchial carcinomas ranged from 1.7 to 10 cm in largest diameter. Follow-up periods varied from 6.8 to 63 months (median: 22 months for metastases and 18 months for NSCLC). Local control was achieved with 94% of NSCLC and 87% of metastases. No serious symptomatic side effects were observed. According to the Kaplan-Meier method the overall survival probability rates of patients with lung metastases were as follows: 1 year: 97%, 2 years: 73%, 3 years: 42%, 4 years: 42%, 5 years: 42% (median survival: 26 months); of those with NSCLC: 1 year: 83%, 2 years: 63%, 3 years: 53%, 4 years: 39%: (median survival: 20.4 months). CONCLUSION: Non-fractionated single-dose irradiation of metastases in the lungs or of small, peripheral bronchial carcinomas is an effective and safe form of local treatment and might become a viable alternative to invasive techniques.