Irradiation Modulates the Pharmacokinetics of Anticancer Drugs

NCT ID: NCT01755585

Last Updated: 2014-01-22

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-07-31

Brief Summary

Radiation therapy (RT) is used as an effective local treatment modality to inhibit cell proliferation, induce cell death and suppress tumor growth. To improve the treatment outcome, in terms of both locoregional control and survival, the concurrent use of chemotherapy during radiation therapy (CCRT) is now the standard treatment for various malignancies, especially locally advanced cancers. Among the drugs used to enhance RT effect, 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents of CCRT.

In the past, RT was solely used as a local treatment and its effect was estimated by local effect model. However, growing evidence shows that irradiation has direct DNA damage-dependent effects as well as sending signals to neighboring cells. Recently, we reported that abdominal irradiation could significantly modulate the systemic pharmacokinetics of 5-FU at 0.5 Gy, off-target area in clinical practice, and at 2 Gy, the daily treatment dose for target treatment in an experimental rat model. Additionally, the results from a clinical investigation showed that colorectal cancer patients with lower AUC of 5-FU during adjuvant chemotherapy had lower disease-free survival. Taken together, these lines of evidence support the importance and necessity to search for the mediators responsible for the unexpected effect of local RT on systemic pharmacokinetics of chemotherapeutic agents, such as 5-FU.

In the present study, the investigators investigated whether the phenomena and mechanism of RT-PK is a fact for different anticancer drugs in human.

Conditions

Rectal Cancer; Cervical Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

C/T-RT group

Chemotherapy (C/T) is applied in the morning. After 2-4 hrs, radiotherapy (RT) is delivered (according to the clinical practice)

No interventions assigned to this group

RT-C/T group

Radiotherapy (RT) is delivered in the morning. After 2-4 hrs, chemotherapy (C/T) is applied (according to the clinical practice).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• World Health Organization (WHO) performance status of 0 or 1
• Age 18-80 years
• Locally advanced rectal cancer
• Locally advanced cervical cancer

Exclusion Criteria

• Cancer history
• Abnormal liver and renal disease
• Immune disease
• Hematological disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Far Eastern Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Hsieh CH, Hou ML, Chiang MH, Tai HC, Tien HJ, Wang LY, Tsai TH, Chen YJ. Head and neck irradiation modulates pharmacokinetics of 5-fluorouracil and cisplatin. J Transl Med. 2013 Sep 26;11:231. doi: 10.1186/1479-5876-11-231.

Reference Type: DERIVED

PMID: 24066670 (View on PubMed)

Other Identifiers

FEMH No. 099148-F

Identifier Type: -

Identifier Source: org_study_id