Carboplatin dosage: prospective evaluation of a simple formula based on renal function.

A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min. Carboplatin plasma clearance was linearly related to GFR (r = 0.85, P less than .

Phase I study of sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors.

Purpose: This phase I dose-escalation study was undertaken to establish the maximum tolerated dose of the sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors. The study also investigated antitumor activity and provided pharmacokinetic and pharmacodynamic data.

Experimental Design: Sixteen patients were assigned sequentially to escalating doses of SJG-136 (15-240 microg/m(2)) given as a 10-minute i.

Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors.

Purpose: A major mechanism of resistance to temozolomide involves the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase). The main aims of this phase I trial were to determine an ATase-depleting dose (ADD) of lomeguatrib, a potent pseudosubstrate inhibitor, and to define a suitable dose of temozolomide to be used in combination with lomeguatrib in patients with advanced cancer.

Experimental Design: Lomeguatrib was administered at dose levels of 10 to 40 mg/m2 days 1 to 5, as a single agent, and also in combination with temozolomide.

Phase I study of TNFalpha AutoVaccIne in patients with metastatic cancer.

We evaluated the safety and immunogencity of a novel vaccine directed against autologous TNFalpha in a Phase I fixed dose escalation trial. The vaccine consisted of two recombinant TNFalpha proteins, with specific peptides replaced by foreign immunodominant T cell epitopes from tetanus toxoid. The main objectives were to establish a safe dose and evaluate the vaccines ability to raise neutralising TNFalpha antibodies.

A cancer research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen.

Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had greater binding affinity for the oestrogen receptor (ER) and reduced agonist activity compared with tamoxifen in preclinical studies. In a randomized phase II trial in 56 postmenopausal patients with progressive locally advanced/metastatic breast cancer we assessed whether idoxifene showed evidence of activity compared with an increased 40 mg/day dose of tamoxifen in patients who had previously demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47 patients eligible for response (25 idoxifene, 22 tamoxifen), two partial responses and two disease stabilizations (SD) for >6 months were seen with idoxifene (overall clinical benefit rate 16%, 95% CI 4.