Adjuvant intravesical therapy for superficial bladder cancer.

OBJECTIVE: To review the results of clinical trials and adverse drug effects of thiotepa, BCG vaccine, mitomycin, and doxorubicin, which are used as adjuvant intravesical therapy for superficial bladder cancer. DATA SOURCE: Information was retrieved from a MEDLINE search, of the English-language literature. Indexing terms included adjuvant pharmaceutics, bladder neoplasms, thiotepa, mitomycin, BCG vaccine, and doxorubicin. DATA EXTRACTION: Data from several human and in vitro studies were assessed and evaluated, according to the strength of comparative data and therapeutic response. STUDY SELECTION: Emphasis was placed on clinical trials that assessed and evaluated dosage, therapeutic regimens, and therapeutic response of adjuvant intravesical therapy for superficial bladder cancer. DATA SYNTHESIS: Adjuvant intravesical therapy and long-term prophylaxis are effective for superficial bladder cancer. Studies have shown that doxorubicin, thiotepa, BCG, and mitomycin, when used as adjuvant therapy, provide better protection than transurethral resection alone against tumor recurrence and prolong the time to when cystectomy is required. CONCLUSIONS: Several randomized clinical trials suggest that BCG is superior to thiotepa, doxorubicin, and mitomycin in preventing bladder tumor recurrence and tumor progression. Local cystitis is an adverse effect produced by all four agents; however, BCG vaccine has been reported to cause a higher incidence of adverse reactions (e.g., dysuria, hematuria). BCG may also cause an influenza-like syndrome, arthralgias, and fever, but most of these reactions have resulted in few severe adverse effects when the drug is given in the relatively modest recommended doses.

Repeated administration of subconvulsant doses of GABA antagonist drugs. II. Effect on monoamine-mediated behaviour.

The effect on monoamine-medical behaviour of repeated daily subconvulsive doses of the GABA antagonist drugs pentylenetetrazol (PTZ) (30 mg/kg for 8 days), picrotoxin (5 mg/kg for 4 days) and bicuculline (3.5 mg/kg for 16 days) was investigated. None of the drugs, administered chronically, increased behavioural responses to the 5-hydroxytryptamine agonist quipazine (25 mg/kg), and neither picrotoxin nor bicuculline altered the locomotor response to the dopamine agonist apomorphine (AP) (0.1 mg/kg). By contrast, repeated doses of PTZ increased the locomotor response to AP, and also increased circling responses to both AP (0.5 mg/kg) and methamphetamine (2.0 mg/kg) in unilateral nigrostriatal-lesioned rats.

Repeated administration of subconvulsant doses of GABA antagonist drugs. I. Effect on seizure threshold (kindling).

Repeated subconvulsant doses of the GABA antagonist drugs picrotoxin (5 mg/kg), pentylenetetrazol (PTZ) (30 mg/kg), and bicuculline (3.5 mg/kg), were given IP once daily to rats. Picrotoxin produced rapid kindling to full seizures in about 5 days, PTZ produced sporadic myoclonic seizures after 17 days, PTZ produced sporadic myoclonic seizures after 17 days whereas bicuculline only produced occasional mild jerking. Following these treatments, seizure thresholds to these drugs were measured by an IV infusion method to minimise problems of systemic uptake and metabolism of the drugs. Picrotoxin- and PTZ-treated animals showed no alteration in seizure threshold. However, following bicuculline pretreatment, seizure threshold was raised. Methodological problems in the interpretation of pharmacological kindling are discussed.