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Martin Reck - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance Pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with Pemetrexed plus cisplatin for advanced nonsquamous non
Current Medical Research and Opinion, 2018Co-Authors: Gary Middleton, Martin Reck, Cesare Gridelli, Filippo De Marinis, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Carla Visseren-grul, Bélen San AntonioAbstract:OBJECTIVES: To assess the effect of long-term Pemetrexed maintenance therapy on patients' renal function. METHODS: In the PARAMOUNT phase III trial (NCT 00789373), Pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of Pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during Pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function. RESULTS: Creatinine clearance ≥45 mL/min was required before the start of any cycle. Patients on Pemetrexed maintenance had a significantly higher percentage maximum increase in sCr over baseline versus placebo for the range of ≥10% to ≥90% increase (p
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phase 2 randomized open label study of ramucirumab in combination with first line Pemetrexed and platinum chemotherapy in patients with nonsquamous advanced metastatic non small cell lung cancer
Cancer, 2015Co-Authors: Robert C Doebele, David R Spigel, Mustapha Tehfe, Sachdev Thomas, Martin Reck, Sunil Verma, J F Eakle, Frederique Bustin, J Goldschmidt, Dachuang CaoAbstract:BACKGROUND Vascular endothelial growth factor (VEGF)–mediated angiogenesis plays an important role in non–small cell lung cancer (NSCLC). Ramucirumab is a human immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2 study investigated ramucirumab in combination with first-line Pemetrexed and platinum chemotherapy in advanced/metastatic NSCLC. METHODS Eligible stage IV nonsquamous NSCLC patients with no prior chemotherapy for metastatic disease were randomized 1:1 to Pemetrexed and carboplatin (or cisplatin) or ramucirumab (10 mg/kg) plus Pemetrexed and carboplatin (or cisplatin) once every 3 weeks. Treatment was given for 4 to 6 cycles, and this was followed by a maintenance phase with Pemetrexed or ramucirumab and Pemetrexed. The primary endpoint was progression-free survival (PFS) with a sample size of sufficient power to detect an increase from 7 to 10.4 months. RESULTS From October 2010 to October 2011, 140 patients were randomized (Pemetrexed-platinum arm, 71; ramucirumab-Pemetrexed-platinum arm, 69), and most baseline characteristics were similar for the 2 treatment arms. The median PFS was 5.6 months for the Pemetrexed-platinum arm and 7.2 months for the ramucirumab-Pemetrexed-platinum arm (hazard ratio, 0.75; P = .132). The objective response rates were 38.0% and 49.3% for the Pemetrexed-platinum and ramucirumab-Pemetrexed-platinum arms, respectively (P = .180). The disease control rate was 70.4% for the Pemetrexed-platinum arm and 85.5% for the ramucirumab-Pemetrexed-platinum arm (P = .032). The grade 3 or higher adverse events occurring in 10% or more of patients were thrombocytopenia, neutropenia, fatigue, anemia, nausea, back pain, and hypertension. CONCLUSIONS The primary endpoint of significant prolongation of PFS was not met; however, ramucirumab showed evidence of clinical activity in combination with Pemetrexed and platinum in nonsquamous NSCLC patients. The addition of ramucirumab to Pemetrexed and platinum did not result in new or unexpected safety findings. Cancer 2015;121:883–892. © 2014 American Cancer Society.
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safety resource use and quality of life in paramount a phase iii study of maintenance Pemetrexed versus placebo after induction Pemetrexed plus cisplatin for advanced nonsquamous non small cell lung cancer
Journal of Thoracic Oncology, 2012Co-Authors: Cesare Gridelli, Martin Reck, Filippo De Marinis, Gary Middleton, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Jesus Corral, Katherine B WinfreeAbstract:Introduction: In a phase III, randomized, double-blind study (PARAMOUNT), maintenance Pemetrexed demonstrated significant benefit in advanced non–small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. Methods: After four 21-day cycles of Pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance Pemetrexed 500 mg/m2 plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). Results: Frequently reported grade 3 to 4 drug-related toxicities with maintenance Pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p 6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance Pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. Conclusions: Long-term use of continuation maintenance Pemetrexed was well tolerated; resource use was low, corresponding with known Pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance Pemetrexed without worsening QoL.
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maintenance therapy with Pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with Pemetrexed plus cisplatin for advanced non squamous non small cell lung cancer paramount a double blind phase 3 random
Lancet Oncology, 2012Co-Authors: Luis Pazares, T P Sahoo, Filippo De Marinis, Jean-louis Pujol, Mircea Dediu, Michael Thomas, P Bidoli, Olivier Molinier, Eckart Laack, Martin ReckAbstract:Summary Background Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from Pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-Pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with Pemetrexed improved progression-free survival after induction therapy with Pemetrexed plus cisplatin. Methods In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction Pemetrexed (500 mg/m 2 ) plus cisplatin (75 mg/m 2 ) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either Pemetrexed (500 mg/m 2 every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373. Findings Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with Pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with Pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49–0·79; p vs none in the placebo group) and febrile neutropenia (five [1%] vs none). Discontinuations due to drug-related adverse events occurred in 19 (5%) patients in the Pemetrexed group and six (3%) patients in the placebo group. Interpretation Continuation maintenance with Pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with Pemetrexed plus cisplatin. Funding Eli Lilly and Company.
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phase iii study of Pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy naive patients with extensive stage small cell lung cancer
Journal of Clinical Oncology, 2009Co-Authors: Mark A Socinski, Martin Reck, Aleksandra Szczesna, Egbert F Smit, Paul Lorigan, Kartik Konduri, Johnetta Blakely, Piotr Serwatowski, Nina Karaseva, Tudor CiuleanuAbstract:Purpose Following a phase II trial in which Pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare Pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). Patients and Methods Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive Pemetrexed-carboplatin (Pemetrexed 500 mg/m2 on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m2 on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of Pemetrexed-carboplatin overall survival with a 15% margin. Results Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, Pemetrexed-carboplatin wa...
Frank V Fossella - One of the best experts on this subject based on the ideXlab platform.
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treatment by histology interaction analyses in three phase iii trials show superiority of Pemetrexed in nonsquamous non small cell lung cancer
Journal of Thoracic Oncology, 2011Co-Authors: Giorgio V Scagliotti, Frances A Shepherd, Thomas Brodowicz, Christoph Zielinski, Johan Vansteenkiste, C Manegold, Lorinda Simms, Frank V FossellaAbstract:Introduction: Recently, histology has emerged as a predictive factor for Pemetrexed efficacy in non-small cell lung cancer (NSCLC). These analyses evaluate whether the differential efficacy of Pemetrexed by NSCLC histology is reproducible and consistent across three registration studies of different lines of therapy (first-line/second-line and maintenance settings). Methods: The reported studies for patients with advanced NSCLC were Pemetrexed versus docetaxel in previously treated patients ( N = 571), cisplatin plus Pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients ( N = 1725), and maintenance Pemetrexed plus best supportive care versus placebo plus best supportive care ( N = 663). Cox models of overall survival (OS) and progression-free survival (PFS) were used to test for a significant treatment-by-histology interaction (THI). A significant THI indicates that the efficacy benefit for Pemetrexed relative to the control arm is greater in patients with nonsquamous histology than in those with squamous histology. Subsequent Cox models were used to estimate hazard ratios for OS and PFS according to histology. Results: Histology was well balanced between treatment arms in each study. Across all three studies, no clinically relevant differences were observed for the safety profile of Pemetrexed among histologic groups. THIs were statistically significant in all three studies for OS ( p = 0.001, 0.002, and 0.033, respectively) and PFS ( p = 0.004, 0.002, and 0.036, respectively). Conclusions: These analyses demonstrate a statistically significant interaction between treatment effect and NSCLC histology, indicating superior efficacy of Pemetrexed in nonsquamous patients compared with other standard treatment options. Thus, histology is consistently predictive of the improved efficacy of Pemetrexed in patients with nonsquamous NSCLC.
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the differential efficacy of Pemetrexed according to nsclc histology a review of two phase iii studies
Oncologist, 2009Co-Authors: Giorgio V Scagliotti, Lorinda Simms, Frank V Fossella, Nasser H Hanna, Katherine Sugarman, Jeremy Blatter, Patrick Peterson, Frances A ShepherdAbstract:BACKGROUND: Recent studies of Pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of Pemetrexed according to histology in two large, phase III NSCLC trials. METHODS: One study tested Pemetrexed versus docetaxel in previously treated patients (n = 571) and the other tested cisplatin plus Pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n = 1,725) with advanced NSCLC. Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (OS) and progression-free survival (PFS). For each histologic subgroup, the Kaplan-Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-adjusted between-arm hazard ratios (HRs). RESULTS: In both studies, treatment arms were well balanced for histology. THIs were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with Pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of Pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups. CONCLUSIONS: The consistency of these results across studies confirms the predictive effect of histology for Pemetrexed and the survival advantage for Pemetrexed in patients with nonsquamous histology. These analyses suggest Pemetrexed should not be recommended for the treatment of squamous cell carcinoma, but, because of efficacy and safety advantages, Pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC.
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the differential efficacy of Pemetrexed according to nsclc histology a review of two phase iii studies
Oncologist, 2009Co-Authors: Giorgio V Scagliotti, Lorinda Simms, Frank V Fossella, Nasser H Hanna, Katherine Sugarman, Jeremy Blatter, Patrick Peterson, Frances A ShepherdAbstract:Background. Recent studies of Pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of Pemetrexed according to histology in two large, phase III NSCLC trials. Methods. One study tested Pemetrexed versus docetaxel in previously treated patients (n 571) and the other tested cisplatin plus Pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n 1,725)withadvancedNSCLC.Coxproportionalhazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (OS) and progression-free survival (PFS). For each histologic subgroup, the Kaplan–Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-adjusted between-arm hazard ratios (HRs). Results.Inbothstudies,treatmentarmswerewellbalanced for histology. THIs were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with Pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of Pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups.
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Pemetrexed in advanced NSCLC: a review of the clinical data.
Oncology (Williston Park N.Y.), 2004Co-Authors: Ralph G Zinner, Frank V Fossella, Roy S HerbstAbstract:The novel multitargeted antimetabolite Pemetrexed (Alimta), recently approved by the US Food and Drug Administration for the treatment of mesothelioma when combined with cisplatin, is also active in first- and second-line non-small-cell lung cancer (NSCLC). In a phase III trial comparing single-agent Pemetrexed vs docetaxel (Taxotere) as second-line therapy in advanced NSCLC, survival was shown to be comparable between these agents, but side effects were significantly less frequent and severe for patients who received Pemetrexed. In the frontline setting, phase II studies have shown significant activity and a very favorable toxicity profile of the combination of Pemetrexed with a platinum agent. Pemetrexed has been well tolerated at systemic doses as a radiosensitizer when given as concurrent chest radiation, and a phase I study is under way to assess its tolerability in combination with carboplatin (Paraplatin) in this setting. Pemetrexed is an important addition to the armamentarium of medicines used to treat thoracic malignancies, and merits study in combination with other drugs having novel mechanisms of action.
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Phase I trials of Pemetrexed.
Seminars in oncology, 2002Co-Authors: Frank V Fossella, Ulrich GatzemeierAbstract:The maximum tolerated dose of the multitargeted antifolate drug Pemetrexed is 600 mg/m(2) every 3 weeks in heavily pretreated patients without folic acid supplementation. However, with folic acid supplementation, higher doses have been given without limiting side effects. The dose-limiting toxicities of Pemetrexed are neutropenia, asthenia, and thrombocytopenia. Other adverse effects include anemia, anorexia, rash, nausea, vomiting, peripheral edema, diarrhea, mucositis, and reversible elevations of transaminase and creatinine levels. Multiple Pemetrexed combination phase I trials have been completed or are underway. Without folic acid supplementation, Pemetrexed doses of 400 to 600 mg/m(2)could be safely administered with full therapeutic doses of irinotecan, gemcitabine, cisplatin, carboplatin, oxaliplatin, and 5-fluorouracil. Preliminary data from other ongoing trials (with folic acid and vitamin B(12) supplementation) have similarly shown that Pemetrexed doses of at least 400 to 500 mg/m(2) can be safely administered with therapeutic doses of vinorelbine, docetaxel, and paclitaxel. Combination studies of Pemetrexed with agents active in breast cancer (doxorubicin, epirubicin, and cyclophosphamide) and chest radiotherapy are also now underway. Adverse effects of these combinations have included neutropenia, anemia, thrombocytopenia, asthenia, vomiting, diarrhea, rash, nausea, anorexia, mucositis, and reversible transaminase elevation. The phase I trials of Pemetrexed have consistently shown activity against a broad range of tumor types, including colorectal cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, and mesothelioma. This activity has been noted not only in the combination trials, but when Pemetrexed is given as a single agent as well. Pemetrexed is a promising drug. It is active against a broad range of cancers, and it has manageable side effects that seem to be lessened with folic acid and vitamin B(12) supplementation.
Filippo De Marinis - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance Pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with Pemetrexed plus cisplatin for advanced nonsquamous non
Current Medical Research and Opinion, 2018Co-Authors: Gary Middleton, Martin Reck, Cesare Gridelli, Filippo De Marinis, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Carla Visseren-grul, Bélen San AntonioAbstract:OBJECTIVES: To assess the effect of long-term Pemetrexed maintenance therapy on patients' renal function. METHODS: In the PARAMOUNT phase III trial (NCT 00789373), Pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of Pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during Pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function. RESULTS: Creatinine clearance ≥45 mL/min was required before the start of any cycle. Patients on Pemetrexed maintenance had a significantly higher percentage maximum increase in sCr over baseline versus placebo for the range of ≥10% to ≥90% increase (p
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safety resource use and quality of life in paramount a phase iii study of maintenance Pemetrexed versus placebo after induction Pemetrexed plus cisplatin for advanced nonsquamous non small cell lung cancer
Journal of Thoracic Oncology, 2012Co-Authors: Cesare Gridelli, Martin Reck, Filippo De Marinis, Gary Middleton, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Jesus Corral, Katherine B WinfreeAbstract:Introduction: In a phase III, randomized, double-blind study (PARAMOUNT), maintenance Pemetrexed demonstrated significant benefit in advanced non–small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. Methods: After four 21-day cycles of Pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance Pemetrexed 500 mg/m2 plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). Results: Frequently reported grade 3 to 4 drug-related toxicities with maintenance Pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p 6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance Pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. Conclusions: Long-term use of continuation maintenance Pemetrexed was well tolerated; resource use was low, corresponding with known Pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance Pemetrexed without worsening QoL.
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maintenance therapy with Pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with Pemetrexed plus cisplatin for advanced non squamous non small cell lung cancer paramount a double blind phase 3 random
Lancet Oncology, 2012Co-Authors: Luis Pazares, T P Sahoo, Filippo De Marinis, Jean-louis Pujol, Mircea Dediu, Michael Thomas, P Bidoli, Olivier Molinier, Eckart Laack, Martin ReckAbstract:Summary Background Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from Pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-Pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with Pemetrexed improved progression-free survival after induction therapy with Pemetrexed plus cisplatin. Methods In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction Pemetrexed (500 mg/m 2 ) plus cisplatin (75 mg/m 2 ) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either Pemetrexed (500 mg/m 2 every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373. Findings Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with Pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with Pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49–0·79; p vs none in the placebo group) and febrile neutropenia (five [1%] vs none). Discontinuations due to drug-related adverse events occurred in 19 (5%) patients in the Pemetrexed group and six (3%) patients in the placebo group. Interpretation Continuation maintenance with Pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with Pemetrexed plus cisplatin. Funding Eli Lilly and Company.
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Pemetrexed in the treatment of advanced non-squamous lung cancer
Lung cancer (Amsterdam Netherlands), 2009Co-Authors: Antonio Rossi, Paolo Maione, Serena Ricciardi, Filippo De Marinis, Cesare GridelliAbstract:Abstract Pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase and other folate-dependent enzymes. Firstly, Pemetrexed was approved in combination with cisplatin for the treatment of malignant pleural mesothelioma. Successively, it has been studied, as single-agent, in phase II and III trials for second-line therapy of non-small cell lung cancer (NSCLC). Based on these results, Pemetrexed has been registered for the treatment of recurrent NSCLC. The next step was to test Pemetrexed plus cisplatin versus gemcitabine plus cisplatin, as first-line therapy in advanced NSCLC patients, in a phase III, non-inferiority, randomized trial. This trial reported the Pemetrexed plus cisplatin regimen to be not inferior, in terms of activity and efficacy, to the control arm but statistically better tolerated. The role of Pemetrexed as maintenance therapy after first-line therapy for advanced NSCLC is currently being evaluated into a phase III trial. The consistency of the results of these recent studies has identified a predictive effect of NSCLC non-squamous histology for Pemetrexed. To date, Pemetrexed is registered, at the dose of 500 mg/m 2 on day 1 of a 3-week schedule, in combination with cisplatin, for first-line therapy and, as single-agent, for second-line treatment of patients with non-squamous NSCLC.This review shows the latest and indicates the future developments of Pemetrexed in the treatment of advanced NSCLC patients.
Cesare Gridelli - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance Pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with Pemetrexed plus cisplatin for advanced nonsquamous non
Current Medical Research and Opinion, 2018Co-Authors: Gary Middleton, Martin Reck, Cesare Gridelli, Filippo De Marinis, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Carla Visseren-grul, Bélen San AntonioAbstract:OBJECTIVES: To assess the effect of long-term Pemetrexed maintenance therapy on patients' renal function. METHODS: In the PARAMOUNT phase III trial (NCT 00789373), Pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of Pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during Pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function. RESULTS: Creatinine clearance ≥45 mL/min was required before the start of any cycle. Patients on Pemetrexed maintenance had a significantly higher percentage maximum increase in sCr over baseline versus placebo for the range of ≥10% to ≥90% increase (p
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safety resource use and quality of life in paramount a phase iii study of maintenance Pemetrexed versus placebo after induction Pemetrexed plus cisplatin for advanced nonsquamous non small cell lung cancer
Journal of Thoracic Oncology, 2012Co-Authors: Cesare Gridelli, Martin Reck, Filippo De Marinis, Gary Middleton, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Jesus Corral, Katherine B WinfreeAbstract:Introduction: In a phase III, randomized, double-blind study (PARAMOUNT), maintenance Pemetrexed demonstrated significant benefit in advanced non–small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. Methods: After four 21-day cycles of Pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance Pemetrexed 500 mg/m2 plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). Results: Frequently reported grade 3 to 4 drug-related toxicities with maintenance Pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p 6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance Pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. Conclusions: Long-term use of continuation maintenance Pemetrexed was well tolerated; resource use was low, corresponding with known Pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance Pemetrexed without worsening QoL.
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Pemetrexed in advanced non-small cell lung cancer.
Expert opinion on drug safety, 2011Co-Authors: Cesare Gridelli, Paolo Maione, Antonio Rossi, Maria Anna Bareschino, Clorinda Schettino, Paola Claudia Sacco, Rosario ZeppaAbstract:Introduction: For patients with advanced NSCLC, treatment outcomes are still disappointing and the search for new active and safe drugs is warranted. The chemotherapeutic agent Pemetrexed has produced, in the last years, an innovation of therapeutic algorithms of this disease, and this review is aimed at describing the role of Pemetrexed in the treatment of NSCLC. Areas covered: In the present review, we discuss the mechanism of action of Pemetrexed, its safety profile and the main clinical data on Pemetrexed in NSCLC treatment. The reader will gain information on Pemetrexed efficacy in the first-line, second-line and maintenance treatment of advanced NSCLC. Moreover, the histotype-based approach to NSCLC treatment, which is important for the selection of patients to be treated with Pemetrexed, is clarified. Expert opinion: The recent introduction of Pemetrexed in the first-line and maintenance treatment of advanced non-squamous NSCLC represents, in our opinion, a significant step forward in the treatment...
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Pemetrexed in the treatment of advanced non-squamous lung cancer
Lung cancer (Amsterdam Netherlands), 2009Co-Authors: Antonio Rossi, Paolo Maione, Serena Ricciardi, Filippo De Marinis, Cesare GridelliAbstract:Abstract Pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase and other folate-dependent enzymes. Firstly, Pemetrexed was approved in combination with cisplatin for the treatment of malignant pleural mesothelioma. Successively, it has been studied, as single-agent, in phase II and III trials for second-line therapy of non-small cell lung cancer (NSCLC). Based on these results, Pemetrexed has been registered for the treatment of recurrent NSCLC. The next step was to test Pemetrexed plus cisplatin versus gemcitabine plus cisplatin, as first-line therapy in advanced NSCLC patients, in a phase III, non-inferiority, randomized trial. This trial reported the Pemetrexed plus cisplatin regimen to be not inferior, in terms of activity and efficacy, to the control arm but statistically better tolerated. The role of Pemetrexed as maintenance therapy after first-line therapy for advanced NSCLC is currently being evaluated into a phase III trial. The consistency of the results of these recent studies has identified a predictive effect of NSCLC non-squamous histology for Pemetrexed. To date, Pemetrexed is registered, at the dose of 500 mg/m 2 on day 1 of a 3-week schedule, in combination with cisplatin, for first-line therapy and, as single-agent, for second-line treatment of patients with non-squamous NSCLC.This review shows the latest and indicates the future developments of Pemetrexed in the treatment of advanced NSCLC patients.
Jean-louis Pujol - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance Pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with Pemetrexed plus cisplatin for advanced nonsquamous non
Current Medical Research and Opinion, 2018Co-Authors: Gary Middleton, Martin Reck, Cesare Gridelli, Filippo De Marinis, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Carla Visseren-grul, Bélen San AntonioAbstract:OBJECTIVES: To assess the effect of long-term Pemetrexed maintenance therapy on patients' renal function. METHODS: In the PARAMOUNT phase III trial (NCT 00789373), Pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of Pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during Pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function. RESULTS: Creatinine clearance ≥45 mL/min was required before the start of any cycle. Patients on Pemetrexed maintenance had a significantly higher percentage maximum increase in sCr over baseline versus placebo for the range of ≥10% to ≥90% increase (p
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safety resource use and quality of life in paramount a phase iii study of maintenance Pemetrexed versus placebo after induction Pemetrexed plus cisplatin for advanced nonsquamous non small cell lung cancer
Journal of Thoracic Oncology, 2012Co-Authors: Cesare Gridelli, Martin Reck, Filippo De Marinis, Gary Middleton, Jean-louis Pujol, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Jesus Corral, Katherine B WinfreeAbstract:Introduction: In a phase III, randomized, double-blind study (PARAMOUNT), maintenance Pemetrexed demonstrated significant benefit in advanced non–small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. Methods: After four 21-day cycles of Pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance Pemetrexed 500 mg/m2 plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). Results: Frequently reported grade 3 to 4 drug-related toxicities with maintenance Pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p 6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance Pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. Conclusions: Long-term use of continuation maintenance Pemetrexed was well tolerated; resource use was low, corresponding with known Pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance Pemetrexed without worsening QoL.
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maintenance therapy with Pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with Pemetrexed plus cisplatin for advanced non squamous non small cell lung cancer paramount a double blind phase 3 random
Lancet Oncology, 2012Co-Authors: Luis Pazares, T P Sahoo, Filippo De Marinis, Jean-louis Pujol, Mircea Dediu, Michael Thomas, P Bidoli, Olivier Molinier, Eckart Laack, Martin ReckAbstract:Summary Background Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from Pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-Pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with Pemetrexed improved progression-free survival after induction therapy with Pemetrexed plus cisplatin. Methods In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction Pemetrexed (500 mg/m 2 ) plus cisplatin (75 mg/m 2 ) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either Pemetrexed (500 mg/m 2 every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373. Findings Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with Pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with Pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49–0·79; p vs none in the placebo group) and febrile neutropenia (five [1%] vs none). Discontinuations due to drug-related adverse events occurred in 19 (5%) patients in the Pemetrexed group and six (3%) patients in the placebo group. Interpretation Continuation maintenance with Pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with Pemetrexed plus cisplatin. Funding Eli Lilly and Company.