3-ap plus cisplatin and paclitaxel in treating patients with advanced or metastatic cancer

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining 3-ap, cisplatin, and paclitaxel in treating patients who have advanced or metastatic cancer.

objectives: * determine the safety and tolerability of 3-ap, cisplatin, and paclitaxel in patients with advanced or metastatic cancer. * determine the toxic effects of this regimen in these patients. * determine the maximum tolerated dose and recommended phase ii dose of this regimen in these patients. * determine the pharmacokinetic parameters of this regimen in these patients. * determine the tumor response in patients treated with this regimen. outline: this is a dose-escalation study. patients receive 3-ap iv continuously over 96 hours on days 1-4 and paclitaxel iv over 3 hours followed by cisplatin iv over 1 hour on day 3. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. patients achieving complete response (cr) receive 1 additional course of therapy after documented cr. patients with partial response or stable disease may receive therapy for up to 6 months. cohorts of 1-6 patients receive escalating doses of 3-ap, paclitaxel, and cisplatin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. projected accrual: approximately 25-30 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed progressive advanced or metastatic cancer * failed 1 or more prior standard therapies for disease or * unlikely to respond to any currently available therapies * measurable or evaluable disease * no active cns metastases * previously treated cns metastases allowed if no evidence of new cns metastases and stable for at least 2 months patient characteristics: age: * 18 and over performance status: * ecog 0-1 life expectancy: * more than 3 months hematopoietic: * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 10 g/dl (transfusion allowed) * no active bleeding or coagulation disorder (occult blood for gastrointestinal cancer allowed) hepatic: * bilirubin no greater than 1.5 mg/dl * alt/ast no greater than 3 times upper limit of normal (uln) (5 times uln if liver metastases present) * alkaline phosphatase no greater than 3 times uln (5 times uln if liver metastases present) * albumin at least 3.0 g/dl * pt/ptt no greater than 1.5 times uln renal: * creatinine no greater than 1.5 mg/dl cardiovascular: * no active heart disease * no myocardial infarction within the past 3 months * no symptomatic coronary artery disease, heart block, or uncontrolled congestive heart failure pulmonary: * no moderate to severe compromise in pulmonary function other: * no mental deficits and/or psychiatric history that would preclude study * no active infection * no pre-existing severe hearing impairment * no pre-existing grade 2 or greater neuropathy * no prior severe allergic reaction to study drugs * no other life-threatening illness * no chronic toxic effects from prior chemotherapy greater than grade i * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 18 months after study participation prior concurrent therapy: biologic therapy: * concurrent hematopoietic growth factors allowed except if used prophylactically during first course of study therapy chemotherapy: * more than 3 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered * more than 6 months since prior combination cisplatin and paclitaxel * prior cisplatin or paclitaxel as single agents allowed * prior 3-ap allowed endocrine therapy: * not specified radiotherapy: * more than 3 weeks since prior radiotherapy and recovered * concurrent radiotherapy to a single site of progressive disease allowed if site requires treatment within the first course of study therapy surgery: * not specified other: * more than 3 weeks since any therapy for malignancy and recovered * no other concurrent investigational drugs without consent of sponsor

Keywords: unspecified adult solid tumor, protocol specific