A Phase I Study of Induction Carboplatin / Paclitaxel Chemotherapy, Pre-operative Radiotherapy With Gadolinium Texaphyrin (Gd-Tex), and Surgical Resection in Stage IIIA (N2) Non-small Cell Lung Carcinoma.
A Phase I Study of Induction Carboplatin / Paclitaxel Chemotherapy, Pre-operative Radiotherapy With Gadolinium Texaphyrin (Gd-Tex), and Surgical Resection in Stage IIIA (N2) Non-small Cell Lung Carcinoma.
Phase I trial to study the effectiveness of combining carboplatin and paclitaxel, radiation therapy with gadolinium texaphyrin, and surgery in treating patients who have stage IIIA non-small cell lung cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as gadolinium texaphyrin may make the tumor cells more sensitive to radiation therapy. Combining chemotherapy, radiation therapy, and surgery may kill more tumor cells.
OBJECTIVES:
I. Determine and compare the frequency and grade of toxicities with the use of gadolinium texaphyrin as a radiosensitizer at two dose levels during preoperative radiotherapy in patients with stage IIIA non-small cell lung cancer.
II. Measure the tumor, involved lymph nodes, and normal lung concentrations of gadolinium and compare to the image pixel intensity obtained by the 1.5 Tesla MRI in this patient population given this regimen.
OUTLINE: This is a dose escalation study of gadolinium texaphyrin (Gd-Tex).
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
Cohorts of 3-6 patients receive escalating doses of Gd-Tex until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.
Patients are followed at 1 month and then every 4 months for 5 years.
Inclusion Criteria:
Histologically confirmed non-small cell carcinoma of the lung
Surgical staging with mediastinoscopy or anterior thoracotomy required
Performance status - Karnofsky 70-100%
WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin normal
AST no greater than 2.5 times upper limit of normal
Creatinine no greater than 2 mg/dL
Creatinine clearance at least 60 mL/min
No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
FEV greater than 0.8 L
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Weight loss no greater than 10% of total body weight within past 3 months
No evidence of neuropathy
No history of allergy to platinum compounds, paclitaxel, porphyrins, or antiemetics appropriate for administration in conjunction with protocol chemotherapy
No concurrent uncontrolled illness (e.g., active infection)
No medical contraindication to MRI (e.g., pacemaker or aneurysm clip)
No G6PD deficiency
No known history of porphyria
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
No prior chest radiotherapy in area of tumor/nodes
No other concurrent investigational agents