Phase 2 study of pemetrexed plus carboplatin, or pemetrexed plus cisplatin with concurrent radiation therapy followed by pemetrexed consolidation in patients with favorable-prognosis inoperable stage IIIA/B non-small-cell lung cancer.

INTRODUCTION: There is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non-small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed. METHODS: In this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non-small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64-68 Gy over days 1-45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate. RESULTS: From June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5-60.0%); PC: 58.4% (95% CI, 42.6-71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0-64.8%); PC: 55.8% (95% CI, 38.0-70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0-12.6 months); PC: 13.1 months (95% CI, 8.3-not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9-NE); PC: 27.0 (95% CI, 23.2-NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy. CONCLUSIONS: Because of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated.

Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer.

INTRODUCTION: Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-ß) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer. METHODS: Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP). RESULTS: Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank p = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia. CONCLUSION: There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.

Low incidence of neutropenic events in patients with lymphoma receiving first-cycle pegfilgrastim with chemotherapy: results from a prospective community-based study.

BACKGROUND: Most alterations to chemotherapy dose and schedule are because of neutropenic events, which mainly occur in the first chemotherapy cycle. This prospective, community-based study evaluated the effectiveness of pegfilgrastim in patients with lymphoma who were also receiving chemotherapy. PATIENTS AND METHODS: Patients aged > or = 18 years with cancer other than leukemia or myelodysplastic syndromes were eligible, including patients with major comorbidities who were generally not eligible for most clinical trials. Key exclusions were weekly chemotherapy and concurrent radiation therapy. Patients received pegfilgrastim 6 mg approximately 24 hours after chemotherapy in each cycle (up to 8 cycles). Endpoints included neutropenic complications and serious adverse events. RESULTS: This open-label single-arm study enrolled 2249 patients at 319 sites. Of these 2249 patients, 325 patients with non-Hodgkin lymphoma (NHL) and 46 patients with Hodgkin disease were included in the primary analysis set. The median age was 65 years for patients with NHL and 41 years for patients with Hodgkin disease, and 31% and 26% had major comorbidities, respectively. Few patients experienced neutropenic complications, including grade 4 febrile neutropenia (patients with Hodgkin disease: 0 [95% confidence interval (CI), 0-8%]; patients with NHL: 13% [95% CI, 10%-17%]); febrile neutropenia-related hospitalization (patients with Hodgkin disease: 0 [95% CI, 0-8%]; patients with NHL: 10% [95% CI, 7%-14%]), neutropenia-related dose reduction (patients with Hodgkin disease: 0 [95% CI, 0-8%]; patients with NHL: 5% [95% CI, 3%-8%]), and neutropenia-related dose delay (patients with Hodgkin disease: 0 [95% CI, 0-8%]; patients with NHL: 5% [95% CI, 3%-8%]). Serious adverse events were consistent with those observed in patients receiving myelosuppressive chemotherapy. CONCLUSION: Patients with lymphoma receiving myelosuppressive chemotherapy supported by pegfilgrastim experienced few neutropenic complications or neutropenia-related alterations in chemotherapy dose and schedule.

Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer.

PURPOSE: Given the activity and tolerability of pemetrexed/platinum combinations in non-small-cell lung cancer, and the success of novel therapeutic strategies employed in recent extensive-stage small-cell lung cancer (ES-SCLC) trials, a randomized phase II trial was initiated to evaluate the use of cisplatin or carboplatin plus pemetrexed in previously untreated ES-SCLC. PATIENTS AND METHODS: Patients were randomly assigned to receive pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or pemetrexed plus carboplatin area under the concentration curve 5. Treatment was administered once every 21 days for a maximum of six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. RESULTS: Between December 19, 2002, and May 17, 2004, 78 patients were enrolled onto this multicenter trial. Median age was 63 years (range, 46 to 82 years) for cisplatin/pemetrexed and 66 years (range, 47 to 75 years) for carboplatin/pemetrexed. Median survival time (MST) for cisplatin/pemetrexed was 7.6 months, with a 1-year survivorship of 33.4% and a response rate of 35% (95% CI, 20.6% to 51.7%). The MST for carboplatin/pemetrexed was 10.4 months, with a 1-year survivorship of 39.0% and a response rate of 39.5% (95% CI, 24.0 to 56.6). Median time to progression for cisplatin/pemetrexed was 4.9 months and for carboplatin/pemetrexed was 4.5 months. Median dose-intensity (actual/planned dose) was 98.94% for cisplatin and 99.95% for pemetrexed in the cisplatin/pemetrexed group and 93.21% for carboplatin and 98.50% for pemetrexed in the carboplatin/pemetrexed group. Grade 3/4 hematologic toxicities included neutropenia (15.8% v 20.0%) and thrombocytopenia (13.2% v 22.9%) in the cisplatin/pemetrexed and carboplatin/pemetrexed treatment groups, respectively. CONCLUSION: Pemetrexed/platinum doublets had activity and appeared to be well-tolerated in first-line ES-SCLC.