Cisplatin, Gemcitabine, Interferon Alfa, and Hyperthermia in Treating Patients With Advanced Cancer

OBJECTIVES:

- Determine the toxicity and tumor response in patients with metastatic, recurrent, or
refractory malignancies treated with cisplatin, gemcitabine, interferon alfa, and
long-duration, low temperature whole body hyperthermia (LL-WBH).

OUTLINE: This is a dose escalation study of cisplatin.

- Phase I and II: Patients receive gemcitabine IV over 30 minutes on day 1 and 8.
Patients receive cisplatin IV over 6 hours on day 15, followed by subcutaneous
interferon alfa on days 16 and 17. Patients undergo long-duration, low temperature
whole body hyperthermia over 6 hours plus gemcitabine over 30 minutes on day 17.
Courses repeat every 5 weeks in the absence of disease progression or unacceptable
toxicity.

- Phase I: Cohorts of 3-6 patients receive escalating doses of cisplatin until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which at least 2 of 3 or 2 of 6 patients experience dose limiting toxicity. The
MTD of cisplatin is used for phase II study.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed metastatic, recurrent, or refractory carcinoma

- Measurable disease by CT, MRI, or physical examination

- No brain metastases or other CNS disorders

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- At least 12 weeks

Hematopoietic:

- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 90,000/mm^3

- Bone marrow cellularity normal on bone marrow biopsy

- No coagulopathy disorder

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

- SGOT no greater than 2 times upper limit of normal

- PT less than 14 seconds

- PTT less than 35 seconds

- No inadequate liver function (no greater than 20% involvement)

Renal:

- Creatinine no greater than 1.8 mg/dL

- Creatinine clearance at least 45 mL/min

- BUN no greater than 25 mg/dL

Cardiovascular:

- Adequate cardiac function documented by history, physical exam, or stress exercise
test (MUGA or ECHO) with resting blood pressure and heart rate increasing
appropriately with exercise

- LVEF at least 45%

- No prior myocardial infarction

- No symptomatic coronary artery disease

- No angina

- No significant arrhythmia

- No uncontrolled hypertension

- No thromboembolic disease

Pulmonary:

- FEV_1 at least 70% of predicted

- Arterial PO_2 at least 60 mmHg on room air

- No massive (greater than 30% involvement) lung disease

- DLCO greater than 50% of predicted

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception

- HIV negative

- No seizure disorders

- No significant emotional instability

- No history of malignant hyperthermia following general anesthesia

- No other concurrent medical illness that would prevent compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- Prior chemotherapy allowed

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- At least 6 days since major thoracic or abdominal surgery

Other:

- No concurrent cardiac glycosides, antiangina drugs, arrhythmia drugs, anticoagulants,
thrombolytic agents, adrenal corticosteroids, or aspirin