RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different
ways to stop tumor cells from dividing so they stop growing or die. Zoledronate may delay or
prevent the formation of bone metastases. It is not yet known whether chemotherapy is more
effective with or without zoledronate in treating non-small cell lung cancer and preventing
PURPOSE: This randomized phase II trial is studying docetaxel and carboplatin alone to see
how well it works compared to giving docetaxel and carboplatin together with zoledronate in
treating patients with unresectable stage IIIB or stage IV non-small cell lung cancer.
- Compare the proportion of patients without disease progression at 6 months among
patients with unresectable stage IIIB or stage IV non-small cell lung cancer treated
with docetaxel and carboplatin with vs without zoledronate.
- Compare time to disease progression in patients treated with these regimens.
- Compare response rate in patients treated with these regimens.
- Compare time to progression in bone in patients treated with these regimens.
- Compare 1-year overall survival in patients treated with these regimens.
- Compare the safety of these regimens in these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1
of 2 treatment arms.
- Arm I: Patients receive docetaxel IV over 1 hour followed by zoledronate IV over 15
minutes and carboplatin IV over 15 minutes on day 1.
- Arm II: Patients receive docetaxel IV over 1 hour followed by carboplatin IV over 15
minutes on day 1.
In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. After completion of 6 courses of therapy, patients in
arm I who have responding or stable disease are then re-randomized to 1 of 2 arms.
- Arm I: Patients receive zoledronate IV over 15 minutes monthly for 12 months from the
date of the first chemotherapy dose.
- Arm II: Patients receive no further treatment. Patients are followed every 1 or 3
months for 12 months from the date of the first chemotherapy dose.
PROJECTED ACCRUAL: Approximately 250 patients will be accrued for this study.
- Histologically confirmed newly diagnosed non-small cell lung cancer (NSCLC),
including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma
- Unresectable stage IIIB disease, including patients with pleural effusion
- Patients with stage IIIB who are candidates for combined chemotherapy and
chest irradiation are not eligible
- Stage IV disease
- No mixed tumors with small cell carcinoma or aplastic carcinoma
- Measurable disease
- At least one measurable lesion outside a previously irradiated area and
detectable by radiologic studies
- No bone metastases
- No brain metastases unless treated and stable for at least 8 weeks
- 18 and over
- ECOG 0-1
- At least 3 months
- WBC ≥ 1,500/mm^3
- Neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Bilirubin ≤ upper limit of normal (ULN)
- Alkaline phosphatase and AST/ALT must meet criteria for one of the following:
- AST or ALT ≤ 5 times ULN AND alkaline phosphatase ≤ ULN
- AST or ALT ≤1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN
- AST or ALT ≤ ULN AND alkaline phosphatase ≤ 5 times ULN
- No hepatic disease that would preclude prolonged follow-up
- Creatinine clearance > 60 mL/min
- Calcium ≥ 8.0 mg/dL (corrected)
- No renal disease that would preclude prolonged follow-up
- No cardiovascular disease that would preclude prolonged follow-up
- No pulmonary disease that would preclude prolonged follow-up
- No weight loss > 5% within the past 6 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy within the past 5 years except treated melanoma, ductal carcinoma
in situ of the cervix, or other cancer cured by resection alone
- No known hypersensitivity to zoledronate, other bisphosphonates, platinum-containing
compounds, mannitol, or polysorbate 80
- No peripheral neuropathy > grade 1
- No uncontrolled infections
- No uncontrolled type 2 diabetes mellitus
- No disease with influence on bone metabolism, including any of the following:
- Paget's disease
- Uncontrolled thyroid dysfunction
- Uncontrolled parathyroid dysfunction
- No neurologic/psychiatric disease that would preclude prolonged follow-up
- No other medical condition that would preclude study participation
PRIOR CONCURRENT THERAPY:
- Not specified
- No prior first-line chemotherapy
- Prior adjuvant or neoadjuvant treatment (including paclitaxel) for NSCLC is
- Not specified
- See Disease Characteristics
- At least 3 weeks since prior radiotherapy and recovered
- No prior radiotherapy covering > 30% of marrow-bearing areas
- No concurrent radiotherapy
- More than 3 weeks since prior thoracotomy and recovered
- More than 30 days since prior systemic investigational drugs or devices
- More than 1 year since prior bisphosphonates
- No other concurrent bisphosphonates
- No other concurrent osteoclastic bone resorption inhibitors (e.g., calcitonin,
mithramycin, or gallium nitrate)
- No other concurrent investigational drugs or devices
- No other concurrent antineoplastic agents during the treatment phase of study