Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma.

Purpose: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone.

Patients And Methods: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m and cisplatin 75 mg/m on day 1, or cisplatin 75 mg/m on day 1.

Clinical application of a semimechanistic-physiologic population PK/PD model for neutropenia following pemetrexed therapy.

Purpose: The objective of these analyses was to examine the effect of variations in the explanatory factors of neutropenic response, identified by semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) modeling, on clinically important features of the absolute neutrophil count (ANC)-time profile (e.g, the nadir of the ANC [NANC], its timing [T (Nadir)], and the timecourse of recovery [T (Rec)]).

Methods: Correlation analyses were used to evaluate the relationship of NANC, T (Nadir), and T (Rec) as a function of overall systemic exposure (AUC) and each of the covariates contained in the population PK/PD model.

A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy.

Purpose: The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response.

Patients And Methods: Data from 279 patients who received 1,136 treatment cycles without folic acid or vitamin B12 supplementation during participation in one of eight phase II cancer trials were available for analysis. Starting doses were 500 or 600 mg pemetrexed per m2 body surface area (BSA), administered as 10-min intravenous infusions every 21 days (1 cycle).

Measuring quality of life in patients with pleural mesothelioma using a modified version of the Lung Cancer Symptom Scale (LCSS): psychometric properties of the LCSS-Meso.

Health-related quality of life (QOL) assessment is a key component in patient assessment and the development of therapies for malignant pleural mesothelioma. However, no mesothelioma-specific instrument was available. The Lung Cancer Symptom Scale (LCSS), a site-specific instrument used to assess QOL in patients with lung cancer, was identified as an instrument that could be appropriate.

Malignant pleural mesothelioma: update, current management, and newer therapeutic strategies.

The diagnosis and management of malignant pleural mesothelioma are major challenges that often frustrate both patient and clinician alike. Occupational asbestos exposure to crocidolite or amosite forms of the fiber is the most important known risk factor in North America and Western Europe. Other mineral fibers such as erionite, a naturally occurring fibrous zeolite crystal, are associated with mesothelioma in volcanic tuffs of the Cappadocia region of central Anatolia in Turkey.

Adapting the Lung Cancer Symptom Scale (LCSS) to mesothelioma: using the LCSS-Meso conceptual model for validation.

Background: The underpinning conceptual model for the Lung Cancer Symptom Scale (LCSS), an instrument used to assess health-related quality of life in patients with lung cancer, has been described elsewhere. The patient-rated scale of the LCSS was modified slightly for patients with mesothelioma (LCSS-Meso), because no other mesothelioma-specific instrument was available.

Methods: In the current methodologic study, the authors tested the conceptual model for the LCSS-Meso.

Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.

Purpose: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone.

Patients And Methods: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1.

Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.

Purpose: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM).

Patients And Methods: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety.

Pemetrexed safety and dosing strategy.

Pemetrexed is a novel antifolate/antimetabolite that inhibits several folate-dependent enzymes, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide transformylase. As a class, antifolates have been associated with sporadic severe myelosuppression with gastrointestinal toxicity. Although infrequent, a combination of such toxicities carries a high risk of potentially life-threatening complications.

Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy.

The purpose of this study was to identify predictive factors for severe toxicity caused by antifolate-chemotherapy using pemetrexed (ALIMTA, LY231514), as a model. Data on potential predictive factors for severe toxicity from pemetrexed were collected from 246 patients treated between 1995 and 1999. Multivariate stepwise regression methods were used to identify markers predictive of severe toxicity.

Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group.

Objectives: To determine the tolerability and efficacy of daily oral marimastat (BB-2516 in patients with metastatic melanoma and to determine the matrix metalloproteinase (MMP) activity, tumour necrosis, peri- and intra-tumoral fibrosis and tumor inflammation in pre- and post-treatment tumor biopsies.

Patients And Methods: Patients with measurable metastatic melanoma who had received no more than one prior chemotherapy regimen and lesions accessible for biopsy were eligible. The first 18 were treated with 100 mg p.