Know Cancer

forgot password

The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy

Phase 2
18 Years
Not Enrolling
Non Small Cell Lung Cancer, Breast Cancer

Thank you

Trial Information

The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy

Germline polymorphisms are inherited genetic variations present in all cells of the body.
Mounting evidence has shown that genetic polymorphisms in drug metabolizing, transporter and
targets genes are major determinants of response to drugs.

The aims of this study are to compare (i) the toxicity profile and efficacy of
gemcitabine/carboplatin or docetaxel, (ii) the distribution of genes involved in docetaxel
and gemcitabine pathways and (iii) to evaluate the association between pharmacogenetics,
pharmacokinetics and pharmacodynamics in East Asian and Caucasian patients.

To date, most pharmacogenetic strategies are predominantly focused on the role of single
genes, in the regulation of drug metabolism. However, there is clear evidence that treatment
outcomes are under the control of a network of genes, each contributing to the patient's
phenotype. In this study, we propose taking a global approach to include relevant candidate
genes in drug pathways to evaluate the effect of polymorphisms and treatment outcomes. We
have selected two commonly used chemotherapy regimens based on our previous observation of
interethnic variability in treatment outcomes and candidate polymorphisms.

By incorporating pharmacokinetic (drug level, drug elimination etc), pharmacodynamic
(treatment response, survival etc) and pharmacogenetic approaches in clinical trials, it
would enhance our understanding of the inter-individual variability in response and toxicity
to drug treatment, and is the first step towards individualized drug treatment.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed i) AJCC/UICC stage IIIB
or IV non small cell lung cancer and stage IV breast cancer for which docetaxel is
indicated. ii) AJCC/UICC stage IIIB or stage IV non small cell lung cancer for which
gemcitabine/carboplatin is indicated.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>=20 mm with conventional techniques or as >=10 mm with spiral CT scan. See section
11.2 for the evaluation of measurable disease.

- Eligible patients must not have been on previous anticancer therapy including
chemotherapy, radiotherapy, biological therapy, or investigational therapy for at
least 4 weeks before study entry (6 weeks if prior therapy included nitrosoureas or
mitomycin C). Prior neoadjuvant or adjuvant chemotherapy, or chemotherapy given
concurrently with radiotherapy for non- metastatic disease, is allowed if the last
dose last dose was given 6 months or more before study entry.

- Patients eligible for docetaxel should have received at least one prior line of
palliative chemotherapy. Patients eligible for gemcitabine/carboplatin should not
have prior palliative therapies.

- Age >=18 years.

- Life expectancy of greater than 8 weeks.

- ECOG performance status <=2 (Karnofsky >=60%).

- Patients must have normal organ and marrow function as defined below:

- leukocytes >=3,000/mcL

- absolute neutrophil count >=1,500/mcL

- platelets >=100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance >=60 mL/min/1.73 m2 for patients with creatinine
levels above institutional normal

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients should not be receiving any other investigational agents.

- Patients with rapidly progressing brain metastases should be excluded from this
clinical trial because of their poor prognosis. Furthermore they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to docetaxel or gemcitabine.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because docetaxel and gemcitabine are
embryotoxic/fetotoxic with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with docetaxel or gemcitabine, breastfeeding
should be discontinued if the mother is treated with docetaxel or gemcitabine. These
potential risks may also apply to other agents used in this study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment toxicities

Outcome Description:

Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]

Outcome Time Frame:

36 weeks

Safety Issue:


Principal Investigator

Wei Peng Yong, MRCP, MB ChB

Investigator Role:

Principal Investigator

Investigator Affiliation:

National University Hospital, Singapore


Singapore: Domain Specific Review Boards

Study ID:




Start Date:

October 2006

Completion Date:

September 2012

Related Keywords:

  • Non Small Cell Lung Cancer
  • Breast Cancer
  • Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms