A phase II study of docetaxel/carboplatin as secondline treatment in patients with refractory or relapsed SCLC

Small cell lung cancer (SCLC) is diagnosed in approximately 15 % of all the
lung cancer cases. SCLC is recognized by its rapid tumor growth, with a high
chemo- and radio sensitivity, and by its high metastasizing potential. Patients
with extensive-stage disease have a 5-year survival rate of 1% to 2%.
Almost 2/3 of the patients have already extensive disease (ED) upon
diagnosis.The recommended treatment of ED-SCLC is systemic chemotherapy,
considered to be the standard first line treatment option in all patients with
SCLC regardless of performance status and age. World-wide, the most commonly
used regimen for 1st line treatment is the combination of cisplatin-etoposide,
while in the Netherlands the cyclophosphamide, doxorubicin and etoposide
regimen is widely used.Survival outcome with these regimens appear similar.
Unfortunately, relapses occur in all patients and responses to second-line
chemotherapy have proven to be of
short term. Until recently, there were no registered drugs for treatment of
relapsing SCLC. Phase II studies with docetaxel in first line - and second line
treatment of SCLC demonstrated that docetaxel is an active agent in these
patient groups. Therefore docetaxel seems suitable for evaluation in
combination with other cytotoxic drugs active in this disease. Until now no
studies have been performed with a combination of docetaxel and platinum in
this group of previously treated SCLC patients.
A phase II study in previously untreated patients with SCLC shows that the
combination docetaxel and cisplatin/carboplatin is an active and well tolerated
regimen in extensive SCLC.
Based on the experience in other pre-treated patient populations (for example
ovarian cancer patients) the combination of docetaxel and carboplatin is
associated with neutropenia in up to 60% of patients. In addition,
lung cancer patients are at risk of developing febrile neutropenia (FN). Based
on prior results by Lalami et al
the proportion of patients with recurrent FN after secondary prophylaxis with
G-CSF (for example pegfilgrastim) is expected to be close to 0%. Recently, in
solid tumor patients receiving standard dose chemotherapy,
levofloxacin proved to be an effective and convenient primary prophylactic
strategy. However, the efficacy of levofloxacin as secondary prophylactic
strategy is not known.

To evaluate the anti-tumor activity of a docetaxel/carboplatin regimen in
patients with refractory or relapsed SCLC. Furthermore to asses the safety
profile of the docetaxel/carboplatin combination.
In patients who have experienced FN, the efficacy of pegfilgrastim and
levofloxacin with regard to secondary prophylaxis will be compared.

This study will be a open label non-randomized study conducted in patients with
refractory or relapsed SCLC.
It is a phase II study with 50 patients.
Docetaxel infusion 75 mg/m2 , carboplatin AUC = 6 mg/ml•min day 1, every 21
days for 4-6 cycles.
Patients experiencing FN will be randomized (1:1) to receive prophylaxis with
pegfilgrastim (Neulasta®) 6 mg once per cycle on day 2 or levofloxacin 500 mg
orally OD for 7 days (day 2-8) during the following cycles.

Docetaxel infusion 75 mg/m2 , carboplatin AUC = 6 mg/ml•min day 1, every 21
days for 4-6 cycles

Hospital visits and tests are not different from the standard treatment. Stress
due to adverse events is not
essential higher estimated. Special risks are not expected. Frequently medical
examination and control of laboratory results will be done. Detailed
instruction will be given about what do to in case of serious toxicity.