2-Drug Combination Chemotherapy Followed by Radiotherapy. Paclitaxel, TAX, NSC-125973;
Cisplatin, CDDP, NSC-119875; followed by chest irradiation using 4-15 MV photons.
This is a Phase II study of paclitaxel administered as a 96-hour (4 day) continuous infusion
with a bolus of cisplatin followed by chest radiotherapy for previously untreated patients
with stage III non-small cell lung cancer (NSCLC). The non-small cell lung cancer tissue
obtained prior to the start of treatment will be studied for mutations of the p53 gene. The
goal of this phase II study is to determine the response rate to 4 cycles of infusional
paclitaxel and bolus cisplatin for patients with stage III NSCLC. The response will again
be assessed following completion of 6000 cGy of chest radiotherapy and the patients will
then be followed for survival. The relationship between the presence or absence of a p53
mutation and the sensitivity of the patient's tumors to paclitaxel plus cisplatin and chest
radiation will be studied. In addition, the plasma levels of paclitaxel will be measured,
and the in vitro paclitaxel chemosensitivity of the tumor cells will be determined from as
many patients as possible. This will allow further study of the relationship between p53
status, in vitro drug sensitivity, achievable plasma concentrations of paclitaxel, and
patients' response to therapy.
Histologically confirmed non-small cell lung cancer of the following histologies: Squamous
cell carcinoma, Adenocarcinoma, Large cell carcinoma, No mixed small/non-small cell
carcinoma with predominant small cell component.
Unresectable stage IIIA/B disease confined to thorax including:
Microscopic disease involvement following attempted surgery and limited to anatomic areas
corresponding to stage III disease (N2-3, T3-4).
Surgically treated stage I/II disease with histologic or cytologic proof of relapse and
limited to anatomic areas corresponding to stage III disease (N2-3, T3-4).
T3, N0 tumor extending directly to the chest wall considered resectable and not eligible.
No stage IIIB disease with pleural effusion visible on chest x-ray unless related to a
No typical carcinoid or mesothelioma.
Measurable disease preferred but not required.
No prior chemotherapy or thoracic radiotherapy.
Age: 18 and over.
Performance status: ECOG 0-2.
AGC greater than 2,000.
Platelets greater than 100,000.
Hepatic: Bilirubin no greater than 1.5 mg/dL.
Renal: Creatinine no greater than 1.5 mg/dL.
No symptomatic heart disease including: Less than fully compensated congestive cardiac
failure, Significant arrhythmias e.g.: Greater than first-degree heart block,
Uncontrolled and symptomatic atrial dysrhythmia except sinus, bradycardia or sustained
ventricular tachycardia, Myocardial infarction within 3 months.
Pulmonary: No major uncontrolled active infection (unless due to obstructed bronchus).
No major active psychiatric problem requiring hospitalization or psychotropic medication
such as phenothiazines.
No prior second malignancy within 5 years except: nonmelanomatous skin cancer, In situ
carcinoma of the cervix.
No pregnant or nursing women.