Table 4.

Clinical Trials of KF

effect	model	results	refs
efficacy	phase I study in patients with  androgen-refractory prostate cancer  in which KF (20–930 mg/m2)  was administered as a daily 1 h  intravenous infusion  for 5 days every 3 weeks	Thirty-three patients were treated; one patient  showed a significant decrease in PSA level (>50%)  associated with clinical improvement (pain relief),  while three patients exhibited stable disease for 2 (n = 2) or  7 (n = 1) months. The MTD was 560 mg/m2/day.	84
efficacy	phase I study in patients with  various solid tumors in  which KF was administered as a  continuous weekly 1 h  intravenous infusion at doses  ranging from 266 to 1200 g/m2	Twenty-five patients were treated, and three patients  achieved a clinical benefit: one hepatocarcinoma patient  who received 24 infusions consisting of 400 g/m2/week, one  squamous carcinoma cavum patient who received nine  infusions at the same dose, and one NSCLC patient who received  16 infusions at a dose of 530 g/m2/week. The MTD was  1200 g/m2/week.	85
safety	two phase I trials in which 60 cancer  patients were administered KF as  a 1 h intravenous infusion	Grade 4 AI was consistently the DLT and tended to  coincide with LDH elevation and an ALT:AP ratio  of >5.0, indicating hepatocellular damage; these  effects were reversible and dose-dependent.	89
safety and  efficacy	phase I study in patients with advanced  solid tumors in which KF was  administered weekly as a 1 h  intravenous infusion at a starting  dose of 266 g/m2/day	Thirty-eight patients were enrolled and received once-weekly  KF 1 h infusions at doses between 266 and 1200 g/m2. Dose-limiting  toxicities included transient grade 3/4 increases in transaminase  blood levels. The maximal tolerated dose for the KF schedule was  800 g/m2, and the recommended dose for phase II studies  was 650 g/m2. No accumulated toxicity was found. This schedule  provided a favorable safety profile and hints of antitumor activity.	86
efficacy  and safety	phase I study in patients with androgen or  metastatic-refractory prostate  cancer in which KF  was administered as a 1 h  intravenous infusion for 5  consecutive days every 3 weeks  with a starting dose  of 20 g/m2/day	Thirty-two patients were treated at nine dose levels (20–930 g/m2/day).  The maximal tolerated dose on this schedule was 930 g/m2/day.  The recommended dose for phase II studies is 560 g/m2/day.	83
efficacy  and safety	phase II study in patients with advanced  malignant melanoma (AMM) in  which KF  was administered weekly as  a 1 h intravenous  infusion with a dose of 650 g/m2	Twenty-four patients were recruited. No objective responses  were observed, but the duration of stable disease suggested some  degree of antitumor activity.	87
response, safety,  and tolerability	phase II study in patients with advanced  non-small-cell lung cancer (NSCLC) in  which KF was administered weekly as a 1 h  intravenous infusion with a  dose of 650 g/m2	Thirty-one patients were enrolled in this phase II trial. The primary  results for efficacy showed no complete responses. One patient  had a partial response; stability occurred in eight patients and disease  progression in 11 patients. Six patients had stable disease lasting for  more than 3 months. The duration of stable disease suggested some  antitumor activity of KF in this indication, while its toxicity was  clinically negligible.	90
efficacy, safety,  and tolerability	phase II study in patients with  hepatocarcinoma (HC) in which KF  was administered as a 1 h  intravenous infusion  with a dose of 650 g/m2 over 1 h per week  until the disease failed to progress or  unacceptable toxicity	Twenty-two patients were recruited. No objective response was observed.  Stable disease occurred in nine patients with a median duration  of 4.8 months. Median progression free survival was 2.4 months.  KF was well tolerated in this patient population, and stable disease  was the best response observed in previously untreated patients with  hepatocarcinoma (HC).	91