Cisplatin plus pemetrexed, with or without bevacizumab

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

Folic acid (350–1,000 µg PO) was given daily, beginning 1 to 3 weeks before the first chemotherapy dose and continuing daily until 1 to 3 weeks after treatment ended.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

A vitamin B12 injection (1,000 µg intramuscularly) was given 1 to 3 weeks before the first chemotherapy dose and was repeated approximately every 9 weeks until treatment ended.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

In an analysis of all patients who were randomly assigned and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. › In an analysis of all patients who were randomly assigned and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone.

The median survival was 12.1 months in the pemetrexed-plus-cisplatin arm and 9.3 months in the cisplatin-alone arm (P = .020).

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. › In an analysis of all patients who were randomly assigned and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone.

The HR for death of patients in the pemetrexed-plus-cisplatin arm, compared with those in the control arm, was 0.77.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. › In an analysis of all patients who were randomly assigned and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone.

Median time-to-progression was significantly longer in the pemetrexed-plus-cisplatin arm (5.7 months vs. 3.9 months; P = .001).

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

This superiority in the combination arm was also demonstrated in the vitamin-supplemented subgroup.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. › This superiority in the combination arm was also demonstrated in the vitamin-supplemented subgroup.

The median survival was 13.3 months in the combination arm and 10.0 months in the cisplatin-alone arm (P = .051).

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. › This superiority in the combination arm was also demonstrated in the vitamin-supplemented subgroup.

The principal adverse effects of the pemetrexed-plus-cisplatin regimen were myelosuppression, fatigue, nausea, vomiting, and dyspnea.

A randomized phase III trial demonstrated the safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-naive patients with malignant mesothelioma who were not eligible for curative surgery.[4][Level of evidence A1] This trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously [IV] every 21 days). With 456 patients enrolled in the trial, 226 patients received pemetrexed plus cisplatin, 222 patients received cisplatin alone, and 8 patients did not receive therapy.After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.Dexamethasone (4 mg) or an equivalent corticosteroid was given orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. › This superiority in the combination arm was also demonstrated in the vitamin-supplemented subgroup.

Most grade 3 to 4 adverse effects were significantly reduced by vitamin supplementation, without any decrease in efficacy.

A randomized controlled, open-label, phase III trial (IFCT-GFPC-0701 [NCT00651456]) evaluated the addition of bevacizumab to chemotherapy and showed an improved OS with the three-drug regimen.[3] The trial included 448 patients with unresectable malignant pleural mesothelioma who had not received previous chemotherapy. Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had no contraindications to bevacizumab, including the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory agents. Patients were randomly assigned to receive IV pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) (PC) with or without bevacizumab (15 mg/kg) (PCB) in 21-day cycles for up to six cycles, until disease progression or toxic effects were seen.Combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy.

A randomized controlled, open-label, phase III trial (IFCT-GFPC-0701 [NCT00651456]) evaluated the addition of bevacizumab to chemotherapy and showed an improved OS with the three-drug regimen.[3] The trial included 448 patients with unresectable malignant pleural mesothelioma who had not received previous chemotherapy. Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had no contraindications to bevacizumab, including the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory agents. Patients were randomly assigned to receive IV pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) (PC) with or without bevacizumab (15 mg/kg) (PCB) in 21-day cycles for up to six cycles, until disease progression or toxic effects were seen.Combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy.

The primary outcome was OS in the intention-to-treat population.

A randomized controlled, open-label, phase III trial (IFCT-GFPC-0701 [NCT00651456]) evaluated the addition of bevacizumab to chemotherapy and showed an improved OS with the three-drug regimen.[3] The trial included 448 patients with unresectable malignant pleural mesothelioma who had not received previous chemotherapy. Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had no contraindications to bevacizumab, including the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory agents. Patients were randomly assigned to receive IV pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) (PC) with or without bevacizumab (15 mg/kg) (PCB) in 21-day cycles for up to six cycles, until disease progression or toxic effects were seen.Combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy.

OS was significantly longer with PCB (median, 18.8 months; 95% CI, 15.9–22.6) than with PC (median, 16.1 months; 95% CI, 14.0–17.9; HR, 0.77; 0.62–0.95; P = .0167).

A randomized controlled, open-label, phase III trial (IFCT-GFPC-0701 [NCT00651456]) evaluated the addition of bevacizumab to chemotherapy and showed an improved OS with the three-drug regimen.[3] The trial included 448 patients with unresectable malignant pleural mesothelioma who had not received previous chemotherapy. Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had no contraindications to bevacizumab, including the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory agents. Patients were randomly assigned to receive IV pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) (PC) with or without bevacizumab (15 mg/kg) (PCB) in 21-day cycles for up to six cycles, until disease progression or toxic effects were seen.Combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy.

Overall, 158 of 222 patients (71%) who received PCB and 139 of 224 patients (62%) who received PC had grade 3 to 4 adverse events.

A randomized controlled, open-label, phase III trial (IFCT-GFPC-0701 [NCT00651456]) evaluated the addition of bevacizumab to chemotherapy and showed an improved OS with the three-drug regimen.[3] The trial included 448 patients with unresectable malignant pleural mesothelioma who had not received previous chemotherapy. Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had no contraindications to bevacizumab, including the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory agents. Patients were randomly assigned to receive IV pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) (PC) with or without bevacizumab (15 mg/kg) (PCB) in 21-day cycles for up to six cycles, until disease progression or toxic effects were seen.Combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy. › Overall, 158 of 222 patients (71%) who received PCB and 139 of 224 patients (62%) who received PC had grade 3 to 4 adverse events.

Patients who received PCB had more grade 3 or higher hypertension (51 of 222 [23%] vs. 0) and thrombotic events (13 of 222 [6%] vs. 2 of 224 [1%]) than patients who received PC.[3][Level of evidence A1]