Phase I Clinical and Pharmacokinetic Study of Pemetrexed and Carboplatin in Patients With Malignant Pleural Mesothelioma

Hughes, Andy; Calvert, Paula; Azzabi, Ashraf; Plummer, Ruth; Johnson, Rob; Rusthoven, Jim; Griffin, Melanie; Fishwick, K; Boddy, Alan V.; Verrill, M.; Calvert, Hilary

doi:10.1200/jco.2002.10.073

Cited by 137 publications

(72 citation statements)

References 37 publications

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“…A total of 27 patients were treated with various dose levels of pemetrexed and carboplatin on day 1 of a 21-day schedule (Hughes et al, 2002). In 25 evaluable patients, eight (32%) achieved a partial remmission and 14 experienced stable disease at various dose levels.…”

Section: Antifolatesmentioning

confidence: 99%

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Tomek

Manegold

2004

Lung Cancer

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This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II -III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine -applied as a single agent or in combination with cisplatin -as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.

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Section: Antifolatesmentioning

confidence: 99%

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Tomek

Manegold

2004

Lung Cancer

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“…In clinical practice, carboplatin is often substituted for cisplatin due to its reduced risk of toxicity (46). Phase II data demonstrated the efficacy of pemetrexed (500 mg/m 2 ) plus carboplatin AUC 5 in MPM (47-49).…”

Section: Combination Of Pemetrexed Added To Platinum Therapymentioning

confidence: 99%

Novel systemic therapy against malignant pleural mesothelioma

Mancuso

Neal

2017

Transl. Lung Cancer Res.

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Malignant pleural mesothelioma is an aggressive tumor of the pleura with an overall poor prognosis. Even with surgical resection, for which only a subset of patients are eligible, long term disease free survival is rare. Standard first-line systemic treatment consists of a platinum analog, an anti-metabolite, and sometimes anti-angiogenic therapy, but there is currently no well-established standard therapy for refractory or relapsed disease. This review focuses on efforts to develop improved systemic therapy for the treatment of malignant pleural mesothelioma (MPM) including cytotoxic systemic therapy, a variety of tyrosine kinase inhibitors and their downstream effector pathways, pharmacologic targeting of the epigenome, novel approaches to target proteins expressed on mesothelioma cells (such as mesothelin), arginine depletion therapy, and the emerging role of immunotherapy. Overall, these studies demonstrate the challenges of improving systemic therapy for MPM and highlight the need to develop therapeutic strategies to control this disease.

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“…Radiation therapy has been shown to alleviate pain in the majority of treated patients, but the duration of symptom control is short lived, hence chemotherapy is generally the treatment of choice. Clinical trials have shown a partial response rate of 32% using a combination of pemetrexed and carboplatin (Hughes et al, 2002). A phase III trial using pemetrexed with cisplatin significantly improved response rates, time to progression, overall survival and quality of life, compared with single agent cisplatin, and suggested that this be used as front-line chemotherapy in MPM patients (Vogelzang et al, 2003).…”

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confidence: 99%

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

et al. 2010

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BACKGROUND: The standard treatment of choice for malignant pleural mesothelioma is chemotherapy with pemetrexed and platinum, but the clinical outcome is poor. This study investigates the response to pemetrexed in a panel of eight mesothelioma cell lines and the clinical outcome for patients treated with pemetrexed in relation to folate receptor alpha (FRa). METHODS: Cell lines were treated with pemetrexed to determine the concentration that reduced growth to 50% (GI 50 ). FRa expression was determined by western blotting and that of FRa, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) by real-time quantitative RT -PCR. Immunohistochemistry for FRa was carried out on 62 paraffin-embedded samples of mesothelioma from patients who were subsequently treated with pemetrexed. RESULTS: A wide range of GI 50 values was obtained for the cell lines, H2452 cells being the most sensitive (GI 50 22 nM) and RS5 cells having a GI 50 value greater than 10 mM. No FRa protein was detected in any cell line, and there was no relationship between sensitivity and expression of folate transporters. FRa was detected in 39% of tumour samples, generally in a small percentage of cells. There was no correlation between the presence of FRa and the outcome of pemetrexed treatment, and no significant difference between histological subtypes. CONCLUSION: Response to treatment with pemetrexed does not depend on the presence of FRa.

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Phase I Clinical and Pharmacokinetic Study of Pemetrexed and Carboplatin in Patients With Malignant Pleural Mesothelioma

Abstract: The MTD was pemetrexed 500 mg/m(2) and carboplatin AUC 6 mg/mL.min. The recommended phase II dose of the combination is pemetrexed 500 mg/m(2) and carboplatin AUC 5 mg/mL.min. The combination is both active and well tolerated in MPM and deserves further exploration.

Cited by 137 publications

References 37 publications

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

Novel systemic therapy against malignant pleural mesothelioma

The role of folate receptor alpha (FRα) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy

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