[Phase I clinical trials in oncology: ethical issues].

The scientific goal of phase I clinical trials in oncology is to determine and optimise the drug dose and schedule on the basis of the toxicity profile. These trials also respond to a need: they offer the chance of early access to a new therapy for cancer patients who are characterised by both the lack of a therapeutic option and a desire to fulfil personal ambitions. The therapeutic relationship in this context must reconcile unreasonable hopes and anxiety regarding death and follow the same rules as in other doctor-patient relationships, with the triple requirement being that it should be genuine, therapeutic and empathetic.

Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients.

Purpose: We performed a Phase I and pharmacokinetic study to determine the maximum tolerated dose of irofulven (6-hydroxymethylacylfulvene; MGI-114, MGI PHARMA, Inc.), administered in intermittent weekly schedules in patients with advanced solid tumors.

Experimental Design: Three schedules were tested: A, days 1, 8, and 15 every 4 weeks; B, days 1 and 8 every 3 weeks; C, days 1 and 15 every 4 weeks.

Protection against oxaliplatin acute neurosensory toxicity by venlafaxine.

Venlafaxine (Effexor; Wyeth Lederlé) has previously shown therapeutic effects for the management of chronic and neuropathic pains. We report here the efficacy of venlafaxine upon acute neurosensory symptoms secondary to oxaliplatin toxicity. A dose of 50 mg of venlafaxine was given orally at the beginning of the oxaliplatin infusion.

Dramatic recovery of paclitaxel-disabling neurosensory toxicity following treatment with venlafaxine.

Venlafaxine is an antidepressant which acts through the inhibition of the reuptake of norepinephrine and serotonin. Venlafaxine is active against neuropathic and chronic pain. We report the case of a 69-year-old woman who presented a paclitaxel-induced neuropathy.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine), an antimetabolite that poisons topoisomerase I.

Purpose: Gemcitabine-containing regimens are among standard therapies for the treatment of advanced non-small cell lung,pancreatic, or bladder cancers. Gemcitabine is a nucleoside analogue and its cytotoxicity is correlated with incorporation into genomic DNA and concomitant inhibition of DNA synthesis. However, it is still unclear by which mechanism(s) gemcitabine incorporation leads to cell death.

Combination of topotecan and oxaliplatin in inoperable hepatocellular cancer patients.

Unresectable hepatocellular carcinoma (UHCC) is considered a chemoresistant disease. Moreover, because the liver underlies the disease, it decreases the tolerance to anticancer agents. Topotecan has shown some clinical activity in UHCC using the 5 days every 3 weeks schedule but is limited by severe hematotoxicity.