Are Serial CA 19-9 Kinetics Helpful in Predicting Survival in Patients with Advanced or Metastatic Pancreatic Cancer Treated with Gemcitabine and Cisplatin?

Abstract

Background: Serial kinetics of serum CA 19-9 levels have been reported to reflect response and survival in patients with pancreatic cancer undergoing surgery, radiotherapy, and chemotherapy. We prospectively studied serial kinetics of serum CA 19-9 levels of patients with locally advanced or metastatic disease treated with gemcitabine and cisplatin. Patients and Methods: Enrolled in the study were 87 patients (female/male = 26/61; stage III/IV disease = 24/63). Patients received gemcitabine 1,000 mg/m² on days 1, 8, and 15 plus cisplatin 50 mg/m² on days 1 and 15, every 4 weeks. Serum samples were collected at the onset of chemotherapy and before the start of a new treatment cycle (day 28). Results: 77 of 87 patients (88.5%) with initially elevated CA 19-9 levels were included for evaluation. According to imaging criteria, 4 (5.2%) achieved a complete remission and 11 (14.3%) achieved partial remission, yielding an overall response rate of 19.5%. 43 (55.8%) patients were CA 19-9 responders, defined by a ≧ 50% decrease in CA 19-9 serum levels within 2 months after treatment initiation. Except for one, all patients who had responded by imaging criteria (n = 14) fulfilled the criterion of a CA 19-9 responder. Despite being characterized as non-responders by CT-imaging criteria (stable/progressive disease), 29 patients were classified as CA 19-9 responders (positive predictive value 32.5%). Independent of the response evaluation by CT, CA 19-9 responders survived significantly longer than CA 19-9 nonresponders (295 d; 95% CI: 285–445 vs. 174 d; 95% CI: 134–198; p = 0.022). Conclusion: CA 19-9 kinetics in serum serve as an early and reliable indicator of response and help to predict survival in patients with advanced pancreatic cancer receiving effective treatment with gemcitabine and cisplatin.

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

“…This biomarker response was in fact the only independent predictor of survival in a multivariate analysis, showing a greater level of significance than either objective tumour response or clinical benefit response (Ziske et al, 2003). Heinemann and colleagues, meanwhile, collected CA19-9 data from patients with advanced pancreatic cancer receiving treatment on a study protocol using a combination of cisplatin and gemcitabine (Stemmler et al, 2003). CA19-9 responders, defined as those with a X50% decrease in CA19-9 levels within 2 months after the start of treatment, survived significantly longer than CA19-9 nonresponders (295 vs 174 days, P ¼ 0.022).…”

Serum CA 19-9 as a Biomarker for Pancreatic Cancer—A Comprehensive Review

“…Whether serum CA 19-9 levels can be used as a surrogate marker of response to chemotherapy has been studied in a variety of clinical settings [41,44,[53][54][55][56][57][58][59][60][61][62][63][64]. Willett et al measured CA 19-9 serum levels in 42 resectable pancreatic cancer patients receiving neoadjuvant treatment with 5-flourouracil and external beam radiation prior to planned pancreaticoduodenectomy.…”

“…Nearly all studies have demonstrated that a treatment related decline in CA 19-9 serum levels is associated with prolonged survival and is an independent predictor of overall survival [41,44,[53][54][55][56][57][58][59][60][61][62][63][64] (Table 5). Reni et al compared basal CA 19-9 serum levels in 247 advanced pancreatic cancer patients enrolled in five consecutive chemotherapy trials (G, gemcitabine; PEFG, cisplatin, epirubicin, 5-fluorouracil, and gemcitabine; PDXG, cisplatin, docetaxel, capecitabine, and gemcitabine) [60].…”

CA19-9 as a prognostic factor in inoperable pancreatic cancer: the implication for clinical trials

“…Despite a small number of publications suggesting that the tumour marker CA19-9 is an important prognostic variable (Gogas et al, 1998;Halm et al, 2000;Saad et al, 2002;Stemmler et al, 2003;Ziske et al, 2003), none of the large published randomised studies of chemotherapy to date have reported baseline CA19-9 levels.…”