Single Agent Alimta in Poor Performance Status in Non-small Cell Lung Cancer

Pemetrexed is designed to block enzymes in the body that are important for tumor growth.
Pemetrexed is commercially approved for the treatment of NSCLC but not for poor performance
status patients.

If you are found to be eligible to take part in this study, you will receive pemetrexed once
every 3 weeks through a needle in your vein over about 10 minutes. Every 3 weeks is
considered 1 treatment cycle. Once the treatment has started, you will return to the clinic
before every treatment cycle. At these visits, you will have a physical exam, a performance
status evaluation, and routine blood (about 3-4 teaspoons) and urine tests. You will have a
chest x-ray and you will be asked to complete a questionnaire about how you are feeling. You
will also have a CT or MRI scan after Cycle 1 and every odd cycle from then on.

You are required to take folic acid by mouth every day for 5 days before the first dose of
pemetrexed and continuing until 3 weeks after your last dose of pemetrexed. You will also
receive an injection of vitamin B12 into your muscle before your first dose of pemetrexed.
The vitamin B12 injection will be repeated every 9 weeks until 3 weeks after your last dose
of pemetrexed.

You will also to take a few low-dose steroid (dexamethasone) tablets twice a day before
treatment, the day of treatment, and the day after each treatment. These will be taken to
decrease the risk of rash and nausea caused by pemetrexed.

You may continue treatment with pemetrexed until your tumor grows or an unacceptable side
effect occurs. You will be evaluated for symptoms 1-2 times per week while you are receiving
treatment and then 2 weeks after stopping study treatment until 6 months after stopping
treatment.

When you stop treatment on this study, you will have a physical exam, routine blood (3-4
teaspoons) and urine tests, and a chest x-ray. The study doctor may ask you to visit
University of Texas MD Anderson Cancer Center (UTMDACC) or be contacted by phone for
follow-up on how you are doing.

This is an investigational study. The FDA has approved pemetrexed for the treatment of
advanced NSCLC after earlier treatment with chemotherapy, and for the treatment for
malignant mesothelioma in combination with cisplatin. About 70 patients will take part in
this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Histologically or cytologically proven Stage IIIB (T4 lesion due to malignant pleural
or pericardial effusion) or Stage IV. Clinically significant pleural or peritoneal
effusions should be drained prior to dosing.

2. Zubrod PS 2 or PS 3

3. Patients with asymptomatic brain metastases and no requirement for corticosteroids or
anticonvulsants are eligible for this clinical trial.

4. Measurable OR non-measurable disease documented by CT or MRI.

5. Patients may have had regimens. At least 4 weeks need to have elapsed since last chemotherapy or biologic
therapy administration.

6. Prior radiation therapy is permitted; however, at least two weeks must have elapsed
since the completion of prior radiation therapy and patients must have recovered from
all associated toxicities at the time of registration. Measurable or non-measurable
disease must be outside the previous radiation field OR patients with visible
progression or new lesions within the radiation field are eligible.

7. At least two weeks must have elapsed since surgery and patients must have recovered
from all associated toxicities at the time of registration.

8. Creatinine clearance >/= 45 cc/min measured or calculated using the following
formula: Calculated Creatinine Clearance = (140 - age) X WT (kg) X (0.85 if
female)/72 X creatinine (mg/dl) Calculated Creatinine Clearance = (140 - age) X WT
(kg) X (1.00 if male)/72 X creatinine (mg/dl)

9. Absolute neutrophil count (ANC) >/= 1,500/µl

10. Platelet >/= 100,000/µl

11. ALT/AST: wherein may be
12. Bilirubin:
13. Hemoglobin: >/=9.0 x 10^9/L

14. Patient must not be pregnant or breastfeeding. Patients of childbearing potential
agree to practice an effective contraceptive method for the duration of the study.

15. Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines.

16. Men and women, aged >/=18 years.

Exclusion Criteria:

1. Prior treatment with pemetrexed therapy.

2. Patients planning to receive any other concomitant anticancer treatment including
chemotherapy, radiation therapy, biologic agents or any other investigational drugs.

3. Women who are pregnant or breastfeeding may not participate in this trial. All women
of childbearing potential must have a negative pregnancy test within 24 hours prior
to enrolling in the study.

4. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a
5-day period (8-day period for long-acting agents, such as piroxicam).

5. Inability and unwillingness to take folic acid or vitamin B12 supplementation.

6. Inability to take corticosteroids.

7. Prior malignancy except for the following: adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer
from which the patient is currently in complete remission or other cancer from which
the patient has been disease-free for >/= 5 years.