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inoperable tumor treatment at NCI - phase I


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Treating Inoperable Lung Tumors With Heated Chemotherapy Medicine Delivered Solely to the Lung




Bethesda , Maryland, United States


Subjects of this study are cancer patients with lung tumors that cannot be removed by surgery and that have not spread elsewhere in the body. This study will evaluate an experimental surgical treatment called isolated lung perfusion that will treat tumors in the lung with a heated chemotherapy medicine called paclitaxel. The study will help determine whether this use of paclitaxel causes side effects and what dosage is safe.To determine eligibility for the study, patients will undergo a physical exam, chest x-ray, electrocardiogram, and CT scan of chest, abdomen, and pelvis (and head, if necessary). Standard blood tests, including an arterial gas, and pulmonary function tests will be done. The chest x-ray and either arterial blood gas or measurement of blood oxygen level by finger probe will be repeated periodically after surgery. Pregnant or breastfeeding women will be excluded from the study.Subjects will be admitted to the Clinical Center 24 hours before surgery. The operation will be performed under general anesthesia. A catheter passed from a neck vein into an artery in the lung, a catheter in the bladder, and electrodes on the chest will help monitor the fluid status and heart rhythm of the patient. A tube through the mouth into the lungs will let the patient breathe during the operation. An incision will be made down the middle of the chest or across the back to access the lung. The lung's blood supply will be separated from the rest of the body's by using catheters. A pump will flush the lung with fluid containing prostaglandin E to make the blood vessels relax. The pump will then push blood and paclitaxel through the lung for 90 minutes. (Patients entering early in the study will receive smaller doses than those entering later in the study.) Several medicines will be given to prevent an allergic reaction to the paclitaxel. The catheters will then be removed, the blood vessels reconnected, and the chest closed with sutures. The operation will last about 4 hours.


Multifocal primary lung cancers, and unresectable pulmonary metastases cause considerable morbidity and mortality. Although typically not amenable to conventional treatment modalities, these lesions may respond to regional delivery of chemotherapeutic agents at doses which cannot be administered systemically. Preclinical animal studies have revealed a significant pharmacokinetic advantage for paclitaxel administered via hyperthermic retrograde isolated lung perfusion techniques (ILuP) relative to intravenous infusion; no acute toxicity has been observed following perfusion with paclitaxel at levels considerably higher than those achievable by systemic administration in humans. Additional in vitro studies have demonstrated that moderate hyperthermia significantly enhances paclitaxel mediated cytotoxicity in a variety of cancer cell lines, but not cultured normal bronchial epithelial cells.Patients with unresectable primary or metastatic cancers involving the lungs will undergo retrograde isolated lung perfusion (ILuP) with paclitaxel and moderate hyperthermia. The dose of paclitaxel will be escalated using a conventional Phase I study design to determine maximum tolerated dose. Pharmacokinetics, pulmonary and systemic toxicity, as well as response to therapy will be recorded. Results of this trial may support further evaluation of paclitaxel alone or in combination with other agents for regional therapy of patients with unresectable pulmonary neoplasms.

Eligibility Criteria

Histologically or cytologically proven unresectable primary lung cancer, or unresectable pulmonary metastases. Patients with bilateral metastases may be considered for staged lung perfusions (three months apart) to address both sides. Patients with unresectable bronchoalveolar carcinomas, or previously treated primary lung cancer may be considered for ILuP. Patients with prior thoracic surgery are eligible for study.Patients may have disease outside the confines of the thorax, provided the bulk of the disease in the chest clearly is the greatest threat to their survival, and/or the extrathoracic disease is controlled.Patients must have a life expectancy greater than three months.Patients must be 18 years of age or older.Patients must have had no chemotherapy, or biologic therapy for their malignancy within 30 days prior to the lung perfusion.Patients with prior paclitaxel exposure will be eligible for this study.Patients who have received radiation therapy to the chest will be considered eligible provided that six months have elapsed since completion of treatment, and there is no history of, nor current evidence of interstitial lung disease.Patients must have an ECOG performance standard of 0 - 1.Patients must have adequate pulmonary reserve evidenced by Pulmonary Function Tests to tolerate pneumonectomy. Specifically, patients with FEV(1) greater than 80% predicted and DLCO greater than 80% predicted will be eligible. Patients with FEV(1) less than 80% predicted or DLCO less than 80% predicted will be eligible if post-operative FEV(1) and DLCO on the basis of split function V/Q scan equal or exceed 40% predicted. Patients must have an oxygen consumption greater than 50% predicted.Patients must have a resting oxygen saturation greater than 90% and a pCO(2) less than 45 mmHg by arterial blood gas.Patients must have a platelet count greater than 100,000, a Hgb greater than 10 gm/dl, a WBC greater than 3500/ml, a normal PT/PTT, and adequate hepatic function as evidenced by a total bilirubin, and AST and ALT less than 1.5 times upper limit of normal.Creatinine must be less than 1.6.Patients with a history of coronary artery disease, previous transmural myocardial infarction, or congestive heart failure will have cardiology consultation. Patients with fixed defects on thallium scanning and adequate (greater than 40%) ejection fraction will be eligible. Patients with reversible or ischemic defects will be considered for lung perfusion only after cardiology clearance.Patients must be willing to sign an informed consent indicating that they are aware of the neoplastic nature of their illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks.Patients may not have potentially treatable pulmonary metastases from lymphomas or germ cell tumors.Patients may not have biopsy proven interstitial fibrosis, radiation induced pneumonitis, or evidence of significant pulmonary hypertension by history, radiologic, echocardiographic or catheterization studies.Patients may not have intracranial or leptomeningeal metastases.Patients may not have prior exposure to bleomycin, nitrosureas, or Busulfan.Patients must have adequate cardiopulmonary reserve evidenced by any of the following parameters: Resting oxygen saturation less than 90%, abnormal Aa gradient, or pCO(2) greater than 45 by arterial blood gas; FEV(1) and/or DLCO less than 40% predicted, or oxygen consumption less than 50% predicted.Pregnant patients and nursing mothers will be excluded due to the unknown effects of paclitaxel on the developing fetus and nursing infant.Patients may not have active infections.Patients with HIV will be excluded due to the potential risk of opportunistic infection resulting from paclitaxel-induced myelosuppresion.Expected Total Enrollment: 39

Trial Source

Government Database

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