Docetaxel With or Without Infliximab in Treating Weight Loss, Loss of Appetite, and Fatigue in Patients With Unresectable Non-Small Cell Lung Cancer (Infliximab Treatment Discontinued Effective 10/05/05)
Docetaxel With or Without Infliximab in Treating Weight Loss, Loss of Appetite, and Fatigue in Patients With Unresectable Non-Small Cell Lung Cancer (Infliximab Treatment Discontinued Effective 10/05/05)
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop
 tumor cells from dividing so they stop growing or die. Infliximab may improve cancer-related
 weight loss, lack of appetite, and fatigue. It is not yet known whether docetaxel is more
 effective with or without infliximab in preventing weight loss and fatigue in patients with
 advanced cancer. (Infliximab treatment discontinued effective 10/05/05)

 PURPOSE: Randomized phase III trial to determine the effectiveness of docetaxel with or
 without infliximab in preventing weight loss, loss of appetite, and fatigue in patients who
 have unresectable non-small cell lung cancer. (Infliximab treatment discontinued effective
 10/05/05)
OBJECTIVES:

 -  Compare the improvement or stabilization of weight in elderly or poor performance status
 patients with unresectable non-small cell lung cancer treated with docetaxel with or
 without infliximab (infliximab treatment discontinued effective 10/05/05).

 -  Compare appetite and functional status in patients treated with these regimens.

 -  Compare the toxicity of these regimens in these patients.

 -  Compare the augmentation or maintenance of lean tissue in patients treated with these
 regimens.

 -  Compare the response rates and time to disease progression in patients treated with
 these regimens.

 -  Compare the survival of patients treated with these regimens.

 -  Determine whether the tumor necrosis factor-alpha polymorphisms in the -308 and -238
 regions predict which cancer patients will experience loss of appetite and weight and
 which patients might potentially benefit from infliximab (infliximab treatment
 discontinued effective 10/05/05).

 OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
 are stratified according to weight loss within the past 6 months (0% vs more than 0% to less
 than 5% vs at least 5%), number of prior chemotherapy regimens (0 vs 1 vs more than 1),
 gender, and GBU prognostic index (good vs bad vs unsure).

 -  Part A (non-randomized, single-center portion of study): Five patients receive
 infliximab IV (infliximab treatment discontinued effective 10/05/05) over 2 hours once
 weekly on weeks 1, 3, and 5 of the first course and once weekly on weeks 1 and 5 of all
 subsequent courses and docetaxel IV over 1 hour (immediately after completion of
 infliximab infusion [infliximab treatment discontinued effective 10/05/05]) once weekly
 on weeks 1-6 of each course. Treatment repeats every 8 weeks for 2-3 courses in the
 absence of disease progression or unacceptable toxicity.

 If none of the 5 patients experiences any grade 4 or 5 toxicity directly attributable to
 infliximab (infliximab treatment discontinued effective 10/05/05), additional patients are
 accrued for part B of the study.

 -  Part B (randomized, multicenter portion of study): Patients are randomized to 1 of 2
 treatment arms.

 -  Arm I (infliximab treatment discontinued effective 10/05/05): Patients receive
 infliximab and docetaxel as in part A.

 -  Arm II: Patients receive docetaxel as in part A and placebo IV over 2 hours
 according to the infliximab schedule in part A (infliximab treatment discontinued
 effective 10/05/05).

 Treatment in both arms repeats as in part A.

 Quality of life, fatigue, appetite/anorexia, cachexia, and weight are assessed at baseline,
 weekly on weeks 1-8, and then monthly for the remainder of study treatment.

 Patients are followed every 6 months for 5 years.
DISEASE CHARACTERISTICS:

 -  Histologically or cytologically confirmed unresectable non-small cell lung cancer that
 is considered incurable with other therapies

 -  Chemotherapy naive or previously treated disease

 -  Meets one of the following criteria:

 -  Age 65 and over with ECOG performance status of 0-2

 -  Under age 65 with ECOG performance status of 2

 -  No symptomatic or known untreated brain metastases

 PATIENT CHARACTERISTICS:

 Age:

 -  See Disease Characteristics

 -  Adult

 Performance status:

 -  See Disease Characteristics

 -  ECOG 0-2

 Life expectancy:

 -  At least 3 months

 Hematopoietic:

 -  Absolute neutrophil count ≥ 1,500/mm^3

 -  Platelet count ≥ 100,000/mm^3

 Hepatic:

 -  Bilirubin normal

 -  AST and/or ALT ≤ 2.5 times upper limit of normal (ULN) if alkaline phosphatase less
 than ULN OR

 -  Alkaline phosphatase ≤ 4 times ULN if ALT less than ULN

 -  No ascites

 Renal:

 -  Creatinine ≤ 1.5 times ULN

 Cardiovascular:

 -  No prior or concurrent congestive heart failure

 Pulmonary:

 -  No prior tuberculosis or positive purified protein derivative skin test (tuberculin
 test)

 Other:

 -  No prior anaphylactic reaction to any taxane

 -  No known mechanical obstruction of the alimentary tract, malabsorption, or intractable
 vomiting (more than 5 episodes per week)

 -  No infection or chronic debilitating illness that would increase the risk of
 chemotherapy administration

 -  No grade 2 or greater peripheral neuropathy of any etiology

 -  No edema

 -  No other malignancy within the past 5 years except adequately treated basal cell or
 squamous cell skin cancer

 -  Alert and mentally competent

 -  Able to complete questionnaires alone or with assistance

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  See Disease Characteristics

 -  No prior docetaxel for metastatic non-small cell lung cancer

 Endocrine therapy:

 -  At least 1 month since prior adrenal steroids, androgens, progestational agents, or
 appetite stimulants

 -  No concurrent adrenal steroids, androgens, progestational agents, or appetite
 stimulants unless needed (e.g., steroids for CNS metastases)

 -  Concurrent inhaled, topical, or optical steroids allowed

 -  Concurrent short-term dexamethasone around days of chemotherapy administration allowed
 for protection against anaphylaxis and emesis

 Radiotherapy:

 -  More than 3 weeks since prior radiotherapy

 -  No prior radiotherapy to more than 25% of bone marrow

 Surgery:

 -  More than 3 weeks since prior major surgery

 Other:

 -  More than 3 weeks since other prior antineoplastic therapy