Discovery Stage IND EXEMPT Clinical Study - Etoposide Plus Methotrexate and Single Nucleotide Polymorphisms

The usual approach group, after local therapy with surgery, 300 double blind random group
separated SCLC patients currently used the Combined Chemotherapy on ETOPOSIDE INJECTION plus
METHOTREXATE INJECTION, based on precisely sequencing drug targets' genes, it will try to do
following:

- Correlate Topoisomerase II Gene Single Nucleotide Polymorphisms (SNPs) to Using
ETOPOSIDE INJECTION Therapeutic Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate CYP450 3A4 Gene Single Nucleotide Polymorphisms (SNPs) to Using ETOPOSIDE
INJECTION Side Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate Dihydrofolic-Acid Reductase Gene Single Nucleotide Polymorphisms (SNPs) to
Using METHOTREXATE INJECTION Therapeutic Effects of Treating Small Cell Lung Cancer
(SCLC)

- Correlate Dihydrofolate Reductase Gene Single Nucleotide Polymorphisms (SNPs) to Using
METHOTREXATE INJECTION Side Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate Thymidylate Synthetase Gene Single Nucleotide Polymorphisms (SNPs) to Using
METHOTREXATE INJECTION Side Effects of Treating Small Cell Lung Cancer (SCLC)

The study approach group, after local therapy with surgery, 300 double blind random group
separated SCLC patients currently used the Combined Chemotherapy on ETOPOSIDE CAPSULE plus
METHOTREXATE TABLET, based on precisely sequencing drug targets' genes, it will try to do
following:

- Correlate Topoisomerase II Gene Single Nucleotide Polymorphisms (SNPs) to Using
ETOPOSIDE CAPSULE Therapeutic Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate CYP450 3A4 Gene Single Nucleotide Polymorphisms (SNPs) to Using ETOPOSIDE
CAPSULE Side Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate Dihydrofolic-Acid Reductase Gene Single Nucleotide Polymorphisms (SNPs) to
Using METHOTREXATE TABLET Therapeutic Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate Dihydrofolate Reductase Gene Single Nucleotide Polymorphisms (SNPs) to Using
METHOTREXATE TABLET Side Effects of Treating Small Cell Lung Cancer (SCLC)

- Correlate Thymidylate Synthetase Gene Single Nucleotide Polymorphisms (SNPs) to Using
METHOTREXATE TABLET Side Effects of Treating Small Cell Lung Cancer (SCLC)

The detailed methods:

- 1) Detect drug target whole gene precision sequence of everyone patient for all 600
recruited double blind SCLC patients.

- 2) Mutually compare everyone patient drug target whole gene precision sequence for total
600 recruited double blind SCLC patients.

- 3) Calculate drug target gene SNPs in all 600 recruited double blind SCLC patients.

- 4) Correlate everyone patient drug target gene SNP to everyone patient drug efficacy.

- 5) Correlate everyone patient drug target gene SNP to everyone patient drug safety.

- 6) Mutually compare the usual approach group SNPs (300 double blind random group
separated SCLC patients) with the study approach group SNPs (300 double blind random
group separated SCLC patients).

- 7) Confirm the relationship between drug target gene SNPs and drug efficacy.

- Select 600 Small-Cell Lung Cancer (SCLC) Patients

- Duration at least 180 days

- The usual approach group - Recruit 300 double blind random group separated SCLC
patients currently used the Combined Chemotherapy on ETOPOSIDE INJECTION plus
METHOTREXATE INJECTION after local therapy with surgery, like as the usual approach
group.

- The study approach group - Recruit 300 double blind random group separated SCLC
patients currently used the Combined Chemotherapy on ETOPOSIDE CAPSULE plus
METHOTREXATE TABLET after local therapy with surgery, like as the study approach
group.

- Inclusion Criteria:

- 1. Clinical diagnosis of small cell lung cancer

- 2. Clinical biopsy diagnosis of small cell lung cancer

- 3. Suitable for local therapy with surgery

- 4. Random and double blind

- 5. Measurable disease

- 6. Adequate organ functions

- 7. Adequate performance status

- 8. Age 22 years old and over

- 9. Sign an informed consent form

- 10. Receive blood-drawing

- Exclusion Criteria:

- 1. Treatment with other anti-cancer therapies and cannot be stopped currently

- 2. Pregnancy

- 3. Breast-feeding

- 4. The patients with other serious inter-current illness or infectious diseases

- 5. Have more than one different kind of cancer in the same time

- 6. Serious Allergy to Lipids

- 7. Serious Bleed Tendency

- 8. The prohibition of the drug product