Gut Liver.2013 Sep;7(5):611-615.

Phase II Trial of Erlotinib Plus Gemcitabine Chemotherapy in Korean Patients with Advanced Pancreatic Cancer and Prognostic Factors of Chemotherapeutic Response.

Semi Park, Moon Jae Chung, Jeong Youp Park, Jae Bock Chung, Seungmin Bang, Seung Woo Park, and Si Young Song.

Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.

 

Abstract

Background/Aims: Erlotinib and gemcitabine combined chemotherapy is becoming the treatment of choice in ad­vanced pancreatic cancer. We evaluated the effectiveness of treatment with erlotinib plus gemcitabine and the prognostic factors for chemotherapeutic response in Korean pancreatic cancer patients.

Methods: Sixty-nine patients with advanced pancreatic cancer who were treated with daily erlotinib 100 mg orally and gemcitabine 1,000 mg/m2/30 min intrave­nous infusion on days 1, 8, and 15 of each 4-week cycle from 2006 to 2009 were included in this study. This study was a phase II single-center trial.

Results: All 69 patients with advanced pancreatic cancer were chemotherapy-naïve. The objective response rate was 18.8%, and the overall tumor-stabilization rate, including partial response and stable disease, was 49.2%. The median overall sur­vival was 7.7 months (95% confidence interval [CI], 6.0 to 9.4 months). The median progression-free survival was 1.9 months (95% CI, 1.4 to 2.5 months). Prognostic factors for good chemotherapeutic response were good performance status and the presence of skin rash during chemotherapy. Patients with lower performance scores (Eastern Cooperative Oncology Group 3) showed worse che­motherapeutic responses (odds ratio [OR], 7.6; 95% CI, 2.4 to 24.8). Poor responses were predicted by the absence of skin rash during chemotherapy (OR, 3.0; 95% CI, 1.4 to 6.3).

Conclusions: Erlotinib and gemcitabine chemotherapy is a tolerable treatment regimen and has a favorable therapeutic effect in Korean patients with advanced pancreatic cancer.

 

Supplementary

Pancreatic cancer is a devastating disease and one of the major causes of cancer-related deaths worldwide. Only 20% of patients with pancreatic cancer have a resectable state at the time of diagnosis.1 Recently, the incidence of pancreatic cancer has increased in Korea. A modern life style and cigarette smoking are the main factors underlying the increase in incidence of pancreatic cancer in Asian patients.2

 Gemcitabine, purine analog, has become the standard of treatment for advanced pancreatic cancer. However, patients who undergo gemcitabine-based chemotherapy for advanced pancreatic cancer still have an overall survival of under 6 months.3-4

Erlotinib (EGFR- tyrosine kinase inhibitor (TKI)) is an orally bioavailable small molecule that inhibits the enzymatic activity of EGFR by binding at the adenosine triphosphate site of the receptor’s tyrosine kinase region.5-6 EGFR targeting has shown promising results in patients with advanced pancreatic cancer and non-small cell lung cancer (NSCLC).7 Subgroup analysis of previous clinical trials in non-small cell lung cancer showed that East Asian patients responded favorably to EGFR TKIs, gefitinib, or erlotinib.7-9

In a recent randomized phase III trial in patients from Western countries, those with advanced pancreatic cancer treated with erlotinib plus gemcitabine combined chemotherapy showed better survival than those patients that received gemcitabine monotherapy.10

 In this study, we evaluated the effectiveness of treatment with erlotinib plus gemcitabine chemotherapy, and also identified prognostic factors of chemotherapeutic response in Korean patients with advanced pancreatic cancer to see if there is a similar ethnical advantage to treatment as has been demonstrated for non-small cell lung cancers.

Table1. Characteristics of Patients.

tab1(Data are presented as number (%) or median (range).

AJCC, American Joint Committee on Cancer; ECOG, Eastern Coopera­tive Oncology Group.)

 

Table2. Toxicity Profiles during Chemotherapy according to World Health Organization Criteria. The most common symptoms of toxicity were skin rash, diarrhea, and thrombocytopenia. The most common adverse event was skin toxicity (31.8%). One patients developed chemotherapy-related interstitial lung disease (ILD)-like syndrome.

tab2(ILD, Interstitial Lung Disease)

 

Table 3. Prognostic Factors of a Poor Chemotherapeutic Response by multivariate Cox analysis.

tab3(OR, odds ratio; CI, confidence interval; AJCC, American Joint Com­mittee on Cancer; ECOG, Eastern Cooperative Oncology Group)

 

 Figure 1Figure 1. Progression-free survival (PFS) estimated by Kaplan-Meier analysis. Patients were divided into two groups according to their response to chemotherapy. PFS (black line) in good responders (orange line) and in poor responders (green line). The median time to progression of disease was 1.9 months (95% CI, 1.4-2.5). The good responder group showed better progression-free survival than the poor responder group (4.2 vs.1.4 months, p=0.001).

Figure 2Figure 2. Overall survival (OS) estimated by Kaplan-Meier analysis. OS (black line) in patients with skin rash (orange line) and in patients without skin rash (green line). The median overall survival was 7.7 months (95% CI, 6.0-9.4). The overall survival days according to the presence of a skin rash was not significantly different between the two groups in this study (9.1 with a skin rash vs. 6.3 months without a skin rash, p=0.32). Subgroup analysis was performed in the patients with severe skin rash over grade 2 compared to the absence of skin rash. The median overall survival days shows 9.5 months versus 6.3 months (p=0.064).

 

The importance of this study

Despite the inclusion of patients with poor performance status (ECOG 3), the median overall survival of patients included in this trial was 7.7 months, which represents some improvement in survival, consistent with previous phase III gemcitabine and erlotinib trials in Western patients with advanced pancreatic cancer. 10

And, subgroup analysis about treatment prognosis was summarized in Table 3. Most predictable factor about chemotherapeutic response is patient’s performance status, and the next best thing is skin rash.

In conclusion, erlotinib plus gemcitabine chemotherapy is a tolerable treatment regimen and has a favorable therapeutic effect in Korean patients with unresectable advanced pancreatic cancer, similar to EGFR-targeted therapy in Asian patients with non-small cell lung cancer.

 

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