Biomedical subjects

Malcolm Ranson

Publications and source records attributed to Malcolm Ranson.

22 records · Page 2Linked to original sources

PubMed2002

ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial.

PURPOSE: To investigate the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS: This was an open, phase I, escalating multiple-dose tolerability and pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days followed by 14 days off treatment. Dose escalation started at 50 mg/d and continued to 925 mg or until consistent dose-limiting toxicity (DLT) was observed. RESULTS: Sixty-four patients were entered at eight dose levels. The most frequent dose-related grade 1 and 2 adverse events were an acne-like (or folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700 mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half-life was 48 hours (range, 37 to 65). Four of 16 patients with non-small-cell lung cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700 mg/d. Overall, 16 patients remained on study for > or = 3 months, with seven of these patients (five with NSCLC, including three of the patients with partial response) remaining on study for > or = 6 months. CONCLUSION: ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.

Administration, Oral↗

PubMed2002

Perspectives on anti-HER monoclonal antibodies.

The ability of Herceptin to prolong survival in women with HER2-overexpressing breast tumors has proven the concept of using humanized or chimeric monoclonal antibodies (MAbs) for cancer therapy. MAbs have been developed that are specific for many tumorigenic molecules and receptors. They can potentially be used to treat a range of solid tumors. Among the most promising targets for therapy are members of the human epidermal growth factor receptor (HER/ErbB) family, particularly HER1 and HER2. Several MAbs have been produced that are directed against HER1. One of these agents, cetuximab (Erbitux), is now advanced in clinical development. HER2 is also a key target and methods are being investigated to maximize the effect of using MAbs to inhibit this receptor. One approach aims to augment the efficacy of trastuzumab (Herceptin) by coupling it to a chemotherapeutic agent, thus enabling the delivery of cytotoxic therapy at a cellular level. Another opportunity is based on research that shows that HER2 acts as a dimerization partner for other HER receptors and consequently is important in HER-ligand-dependent tumor growth. Therefore, anti-HER2 MAbs that inhibit the association of HER2 with other HER family members have the potential to be highly effective. This article reviews some of these alternative approaches to MAb-based anti-HER therapy that will hopefully improve treatment outcome for patients with a range of solid tumors.

Antibodies, Monoclonal↗

PubMed2002

ZD1839 (IRESSA): a selective EGFR-TK inhibitor.

The recent development of highly selective, target-based cancer therapeutics, such as ZD1839 has resulted from a greater understanding of tumor biology. Amongst the most promising of new target-based agents are inhibitors of the epidermal growth factor receptor. ZD 1839 is a potent, selective epidermal growth factor receptor tyrosine kinase inhibitor that has demonstrated promising results in early clinical trials.

Animals↗

PubMed2002

ZD1839 (Iressa): for more than just non-small cell lung cancer.

ZD1839 (Iressa) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways involved in cell proliferation. Preclinical studies demonstrated that ZD1839 is a promising agent for the treatment of a wide range of tumors and has additive-to-synergistic effects when combined with radiation or chemotherapy in various cell lines and xenografts. Phase I clinical trials have reported that ZD1839 has acceptable tolerability and antitumor activity. In addition to non-small cell lung cancer, phase II/III studies are currently investigating ZD1839 as monotherapy or in combination therapy against prostate, breast, head and neck, gastric, and colorectal tumors.

Antineoplastic Agents↗