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 tirapazamine, carboplatin, and paclitaxel in treating patients who have advanced malignant solid tumors.

OBJECTIVES:

• Determine the maximum tolerated dose of tirapazamine in combination with carboplatin and paclitaxel in patients with advanced solid tumors who have or have not received prior chemotherapy.
• Assess the toxicity and preliminary efficacy of this regimen in these patients.
• Determine the pharmacokinetic profile of this regimen in these patients.
• Investigate potential predictors of response by studying patient tissue specimens after receiving this regimen.

OUTLINE: This is a dose-escalation study of tirapazamine. Patients are stratified according to prior chemotherapy status (previously untreated vs previously treated).

Patients receive tirapazamine IV over 2 hours, paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes. Treatment continues every 21 days for a maximum of 8 courses in the absence of unacceptable toxicity or disease progression. Some patients may continue therapy in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tirapazamine 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. An additional 12 patients in the previously untreated stratum are treated at the MTD.

Patients are followed indefinitely.

PROJECTED ACCRUAL: A total of 36-68 patients (18-34 per stratum) will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced or metastatic malignant solid tumor not curable by resection or other standard therapy

• No symptomatic brain metastases

  • Brain metastases allowed provided controlled with surgical excision and/or radiotherapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,000/mm3
• Absolute neutrophil count at least 1,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2 times upper limit of normal

Renal:

• Creatinine normal
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV congestive heart failure

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study
• No history of allergic reactions to appropriate diuretics or antiemetics administered in conjunction with protocol chemotherapy (e.g., 5-HT3 antagonists)
• No other concurrent uncontrolled illness that would preclude study therapy
• No medical, social, or psychological factors that would preclude study therapy
• No clinically significant hearing loss

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) and recovered
• No more than 2 prior chemotherapy regimens
• No prior combination paclitaxel and carboplatin

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• At least 30 days since other prior investigational drugs
• No other concurrent anticancer therapy
• No other concurrent investigational agents