Trial Information

Phase II Study of Biweekly Schedule of Docetaxel and Cisplatin in Patients With Unresectable Non-small Cell Lung Cancer

Study design is followings: The sample size was calculated according to Simon's two stage
optimal design. Assuming a response rate of 40%, a probability of error of 5% and a power of
80%, a total of 48 patients (43 patients plus 5 patients to compensate a 10% drop-out rate)
were enrolled. In the initial stage, 13 evaluable patients were to be entered into the study
and evaluated for their response. If ≥ 3 responses were observed during the first stage,
then 30 additional patients were to be entered in the second stage. The statistical
evaluation was performed based on the intention to-treat analysis.

The combination chemotherapy consisted of docetaxel of 40mg/m2 as a 1-hour infusion followed
by cisplatin 40mg/m2 as a 30-minutes intravenous infusion and both drugs were given on days
1, and 15 in an outpatient setting. Patients also received adequate hydration with at least
1,500ml of half saline or normal saline before cisplatin administration. All the patients
received antiemetic therapy that consisted of intravenous 5-HT3 antagonist and dexamethasone
before docetaxel administration. The treatment cycles were repeated every 4 weeks until the
maximum six cycles.

The patients whose absolute neutrophil count and platelet count were greater than or equal
to 1.500 and 100,000/mm3, respectively, and who had lower than or equal to grade 1
non-hematologic toxicity (excluding alopecia) received chemotherapy on day 1 of each cycle.

On days 15 of each cycle, the minimum requirements to receive chemotherapy were an absolute
neutrophil count between 1000 and 1,500/mm3, a platelet count ≥75,000/mm3 and no grade ≥2
nonhematologic toxicity (excluding alopecia).

If these conditions were not met on days 1, or 15, then chemotherapy was postponed for 1
week. A delay of more than 3 weeks resulted in withdrawal from the study.

If there were any grade 3 to 4 hematologic toxicities at the nadir of the previous cycle, or
febrile neutropenia with or without documented infection, then administration of both drugs
in the subsequent cycles was reduced by 25% from the planned dose.

The Administration of granulocyte-colony stimulating factor (G-CSF) was allowed in the
presence of febrile neutropenia, and grade 3 or 4 neutropenia.

In the presence of grade 3 or 4 non-hematologic toxicity (except nausea, vomiting and
alopecia), the treatment was postponed until resolution of the toxicity and then both drug
doses were reduced by 25% for the next cycle. Treatment was stopped at any time for
documented disease progression, unacceptable toxicity or according to the patient's own
refusal.

The pretreatment baseline evaluation included a complete medical history and physical
examination, a complete blood cell count (CBC) with the differentials, chemistry profiles
and performance status. Chest X-rays, chest and upper abdominal computed tomography (CT)
scans, brain CT scan or magnetic resonance imaging, a radionuclide bone scan and other
diagnostic procedures were performed as clinically indicated.

During treatment, a limited history taking, physical examination, assessment of toxicity, a
complete blood cell count with the differentials and blood chemistry tests were repeated
weekly. A chest X-ray was performed every 4 weeks before each cycle.

Appropriate imaging studies, including CT scans of the chest and upper abdomen, were
performed every two cycles to assess the treatment response, and sooner if needed for
documenting disease progression. The objective tumor responses were assessed according to
the RECIST criteria. The response rate was calculated as the ratio of the number of patients
who achieved a complete or partial response to the number of enrolled patients. Overall
survival (OS) and Time to progression (TTP) were calculated from the start of therapy until
death and progression, respectively, or until the last follow-up. Toxicities were evaluated
according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale version
3.0.