PDX (pralatrexate) is an injectable small molecule chemotherapeutic agent that has an enhanced potency and toxicity profile relative to methotrexate and other related dihydrofolate reductase, or DHFR, inhibitors.
Dihydrofolate Reductase (DHFR) is a key enzyme in thymidine synthesis and has become a target for drug development and cancer therapy. The variations between DHFR have enabled the development of species-selective DHFR inhibitors, such as trimethoprim (antibacterial and antifungal), pyrimethamine (antiprotozoal), and methotrexate, MTX, (antineoplastic, antipsoriatic, and anti-inflammatory).
Methotrexate, were among the first chemotherapeutic agents discovered and remains one of the most widely applied chemotherapy drugs and has been used to treat breast, bladder and head and neck cancers, leukaemia and other cancers.
The Phase 1 dose escalation study aims to test the safety, tolerability and pharmacokinetics (PK) of escalating doses of PDX. The subject hopes to enroll one to six patients per treatment level who have received one prior chemotherapy regimen and may or may not have received an epidermal growth factor receptor (EGFR) Kinase inhibitor.
Results of an earlier trial published in the June 2003 issue of Clinical Cancer Research demonstrated improved response rate and symptomatic benefits in patients with Stage IIIB or IV NSCLC who received PDX therapy.
Median survival time of patients enrolled in the study was 13.5 months, with 1 and 2-year survival rates of 56 per cent and 36 per cent, respectively. Ten per cent (10 per cent) of PDX-treated patients had confirmed durable responses and 31 per cent had stable disease.
A spokeswoman for AllosTherapeutics told DrugResearcher.com: "Ongoing studies suggest that vitamin supplementation may reduce the number of treatment-related AEs in patients administered antifolates."
"The Phase 2 study did not include vitamin supplementation as part of the treatment plan. The Phase 1 study that was recently initiated is meant to determine whether the addition of vitamin supplementation can reduce the incidence of stomatitis, which in turn would allow for a higher dose."
The spokeswoman mentioned that multi-centre Phase 2 trial of PDX in patients with NSCLC would begin in 2005, once appropriate dosing has been determined.
Lung cancer is the most common cause of cancer death worldwide causing up to 3 million deaths. Most common is bronchogenic carcinoma (about 90 per cent).
Lung cancer is the most lethal malignant tumour worldwide.account for about 14 per cent of all cancer diagnoses. Non-small cell lung cancer is the most common type of lung cancer, accounting for almost 80 per cent of lung cancer cases. More people die of lung cancer than of breast, prostate and colorectal cancers combined.
Worldwide, the cancer causes up to 3 million deaths. Most common is bronchogenic carcinoma (about 90 per cent).