Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Trial of Single-Agent Pemetrexed (Alimta®) Versus the Combination of Carboplatin and Pemetrexed in Patients With Advanced Non-small-cell Lung Cancer and Performance Status of 2
Brief Summary: Optimal management of patients with advanced NSCLC and with PS 2 remains controversial and underrepresented in clinical trials, typically accounting for 5 to 10% of enrolled patients. Patient PS 2 proportion in population-based studies is considerably higher than that included in clinical trials. Management of patients with PS of 2 in clinical practice is empirical and inconsistent. Patients have median overall survival of 3 to 5 months in randomized trials, and treatment options include best supportive care, single-agent and combination chemotherapy. Retrospective studies have suggested that patients PS 2 may benefit from first-line chemotherapy in terms of symptom improvement and overall survival. In many of these studies, single-agent chemotherapy was compared with best supportive care alone. Data on the role of cisplatin-based combinations for patients with PS 2 is more scant, with one study questioning its benefit, and another interrupting accrual because of undue toxicity. With regards to carboplatin, the Cancer and Leukemia Group B (CALGB) study 9730 compared paclitaxel plus carboplatin versus paclitaxel alone in a subgroup of 107 patients with PS 2; the median overall survival was significantly longer in group treated with combination chemotherapy (4.7 versus 2.4 months). Combination chemotherapy with carboplatin and paclitaxel also produced a statistically significantly higher incidence of severe hematological and non-hematological toxicities. On the basis of aforementioned results, a recent European panel stated that carboplatin-based or low-dose cisplatin-based doublets might represent alternative options to single-agent chemoterapy in patients PS 2. Outside clinical trials, single-agent chemotherapy with a 3rd generation agent remains valid option for patients PS2. Results demonstrate that pemetrexed is an agent with established single-agent activity in NSCLC, and suggest it is a potential candidate for combinations with platinum and other agents currently utilized for patients with advanced NSCLC. Favorable toxicity profile of pemetrexed suggests that this agent is an ideal candidate for single agent testing and in combination among patients with PS 2. Substantial doubt remains in the comparative benefit from monotherapy versus combination. Starting dose and schedule of pemetrexed were set for this study based on its current labeling in the 2nd line treatment of metastatic NSCLC and 1st line treatment of malignant pleural mesothelioma.


Options:
A: Inclusion Criteria:

* Newly diagnosed NSCLC in stage IIIB (with a cytologically positive pleural or pericardial effusion) or stage IV, according to the sixth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual37;
* Age \> 18 years;
* No prior chemotherapy, including adjuvant or neoadjuvant therapy, for the treatment of NSCLC;
* Histological confirmation of any non-squamous histological type of NSCLC, given the recent findings of treatment benefit in this population44;
* ECOG performance status of 2;
* At least 3 weeks must have elapsed since major surgery, and at least 1 week since mediastinoscopy, pleuroscopy, or thoracostomy;
* Patients must have measurable disease, defined as lesions that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scan) or as ≥ 10 mm with spiral CT scan;
* Adequate organ function as indicated by the following:

  * White blood cell (WBC) count ≥ 3500/mm3
  * Absolute neutrophil count (ANC) ≥1500/mm3
  * Hemoglobin ≥ 9.0 g/dL
  * Platelet count ≥ 100,000/ mm3
  * Total bilirubin ≤ 2 times the upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN, unless liver metastases present, in which case AST and ALT have to be ≤ 5 times the ULN
  * Estimated glomerular filtration rate (GFR) ≥ 45 mL/min
* Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration;
* Fertile patients (male or female) must agree to use an acceptable method of contraception to avoid pregnancy for the duration of the study and for 3 months thereafter;
* Patients must sign an Informed Consent Form;
* Have the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol requirements;

Exclusion Criteria:

* ECOG performance status other than 2;
* Prior chemotherapy for the treatment of NSCLC;
* Lesions that have been irradiated cannot be included as sites of measurable disease. If the only measurable lesion was previously irradiated the patient cannot be included;
* Symptomatic central nervous system (CNS) metastases. Prior CNS metastases are allowed if the patient is neurologically stable and not receiving corticosteroids;
* Serious uncontrolled intercurrent medical or psychiatric illness;
* Active and ongoing systemic infection;
* Second primary malignancy (except in situ carcinoma of the cervix, in situ carcinoma of the bladder, adequately treated basal-cell carcinoma of the skin, adequately treated squamous-cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior malignancy treated more than 5 years prior to enrollment and without recurrence);
* Known hypersensitivity to pemetrexed;
* known hypersensitivity to carboplatin;
* Pregnancy or lactation;
* Use of any investigational agent within 30 days prior to enrollment into the study;
* Unable to discontinue administration of non-steroidal anti-inflammatory (NSAIDSs) agents for 2 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with short half-life, such as ibuprofen (total of 5 days), in patients with a GFR between 45 and 79 mL/min; and for 5 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with long half-life (total of 8 days, see 7.4.2) in all patients; patients with a GFR ≥ 80 mL/min may receive concomitant study treatment and ibuprofen or aspirin (≤ 1.3 g/day);
* Inability to comply with requirements and procedures of study.
B: DISEASE CHARACTERISTICS:

* Histologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following types:

  * Squamous cell
  * Adenocarcinoma
  * Large cell anaplastic
  * Bronchoalveolar
  * Non-small cell carcinoma not otherwise specified NOTE: Mixed tumors are categorized by the predominant cell type (tumors with small-cell anaplastic elements are ineligible)
* Evidence of at least 1 of the following:

  * Clinically documented recurrent disease after prior radiation or surgery
  * Stage IV disease (distant metastases)
  * Stage IIIB disease presenting with 1 of the following:

    * Pleural or pericardial effusion by CT scan or chest x-ray
    * Pleural implants documented pathologically or seen on CT scan or x-ray
* Measurable or evaluable disease
* No brain metastases unless clinically stable after surgery and/or radiotherapy

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 1.5 mg/dL
* AST less than 5 times upper limit of normal

Renal

* Creatinine no greater than 1.5 mg/dL OR
* Creatinine clearance at least 40 mL/min

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No hypersensitivity to agents that contain Cremophor EL (polyoxyethylated castor oil)

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy for advanced NSCLC

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* Recovered from prior radiotherapy
* No prior radiotherapy to the only site of measurable disease, unless the site had subsequent progression of disease documented by physical exam, radiography, or pathology
* No concurrent radiotherapy (except for brain metastases)

Surgery

* See Disease Characteristics

Other

* No concurrent aminoglycoside antibiotics
C: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC) meeting criteria for 1 of the following:

  * Newly diagnosed selected stage IIIB (T4 lesion due to malignant pleural effusion) disease
  * Newly diagnosed stage IV disease
  * Recurrent disease after prior surgery and/or radiotherapy
* The following cellular subtypes are allowed:

  * Adenocarcinoma
  * Large cell carcinoma
  * Squamous cell carcinoma
  * Unspecified carcinoma
* Measurable or nonmeasurable disease by CT scan, MRI, x-ray, physical examination, or bone scintigraphy

  * Pleural effusions, ascites, and laboratory parameters are not allowed as the only evidence of disease
  * Disease must be present outside area of prior surgical resection
  * Disease must be present outside area of prior radiotherapy OR new lesion documented
* No known brain metastases by CT scan or MRI within the past 6 weeks
* No pleural or pericardial effusions requiring treatment

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute granulocyte count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL

Hepatic

* Bilirubin ≤ 2 times upper limit of normal (ULN)
* SGOT or SGPT ≤ 2 times ULN
* Alkaline phosphatase ≤ 2 times ULN

Renal

* Creatinine ≤ ULN
* Creatinine clearance ≥ 50 mL/min

Cardiovascular

* No uncontrolled hypertension
* No unstable angina
* No congestive heart failure
* No myocardial infarction within the past year
* No ventricular arrhythmia requiring medical intervention

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No prior allergic drug reaction attributed to Cremophor or polysorbate 80
* No disorder associated with lung cancer with life-threatening consequences
* No motor or sensory neuropathy ≥ grade 2
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
* No uncontrolled diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior biologic therapy for NSCLC

Chemotherapy

* No prior systemic chemotherapy for NSCLC

Endocrine therapy

* No prior or concurrent steroid-type hormonal therapy (e.g., ethinyl estradiol)

Radiotherapy

* See Disease Characteristics
* At least 3 weeks since prior radiotherapy and recovered

Surgery

* See Disease Characteristics
* At least 2 weeks since prior thoracic or other major surgery and recovered

Other

* No prior or concurrent azole antifungal therapy (e.g., ketoconazole, miconazole, or itraconazole)
* No prior or concurrent macrolides (e.g., erythromycin or clarithromycin)
* No prior or concurrent cyclosporine, terfenadine, benzodiazepines (e.g., diazepam, triazolam, or midazolam), or retinoids
* No prior or concurrent calcium antagonists (e.g., diltiazem, nifedipine, or verapamil)
D: Inclusion Criteria:

* Pathologically / cytologically proven NSCLC stage IIIB or IV
* age \>= 70 years old and \< 90 years old

Answer: A