HEPATOBILIARY PANCREATIC CANCER: CUTTING-EDGE DRUG THERAPY

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Abstract

Chemotherapy appears to prolong survival in patients with advanced pancreatic cancer (PC) or biliary tract cancer (BTC) and can take clinical benefits and improve quality of life since the clinical use of gemcitabine (Gem) in 1999 in Japan [1].

Many investigators have struggled to prove the superiority of Gem-contained combination therapy to Gem monotherapy for PC patients. Unfortunately, they all failed to prove the better survival benefit except Gem plus Erlotinib (GE) [2]. GE therapy demonstrate to be superior both in metastatic and locally advanced PC (HR 0.81). Many patients with GE therapy suffer from skin rush, and sometimes are afraid of a risk of Interstitial lung diseases (ILD).

French investigators created a new standard chemotherapy which does not contain Gem: FOLFIRINOX. FORFIRINOX regimen can deliver a much better survival benefit rather than Gem monotherapy in metastatic PC, although it increased both hematological and non-hematological adverse effects (AE).

Gem plus S1 (GS) showed both good survival benefits and anti-tumor effect in previous phase II studies [3,4]. We carried phase III study called GEST trial in Japan and Taiwan, which aimed to make sure the superiority of GS to Gem and non-inferiority of S1 to Gem. However, we can prove only non-inferiority of S1 to Gem in OS both in metastatic and locally advanced PC [5].

It is not clear whether radiotherapy should be useful or beneficial for locally advanced PC. Moreover, we do not have a good answer which drug we should administer when we plan the chemoradiotherapy for PC. Currently, there are some randomized phase II studies of chemoradiotherapy for PC in Japan, one is a study of chemoradiotherapy using GS combination compared with GS therapy, and the other is a study of Gem monotherapy followed by S1-chemoradiothrapy compared with S1-chemoradiotherapy. We need a well-designed phase II or phase III trial to prove a benefit of radiotherapy in PC near the future. But it is difficult to standardize a procedure of radiotherapy in many institutions even only in Japan.

Gem plus cisplatin (CisGem) showed a better OS compared with Gem6) in BTC [6]. Kanai et al. study a phase I study of CisGem plus S1 in BTC (KHBO1002) [7].

We need to develop much more chemotherapy or chemoradiotherapy in PC or BTC, because we do not have enough agents to administer and there are many clinical questions still.

references

1. Burris et al. JCO 1997; 15: 2403–13

2. Moore JM. et al. JCO 2007; 25: 1960–66

3. Ueno H. et al. ASCO 2007 abstract #4550

4. Nakamura K. et al. BJC 2006; 94: 1575-79

5. Ioka T. et al. ASCO2011 abstract #4007

6. Valle J. et al. NEJM 2010; 362: 1273-81

7. Kanai M. et al. CCP 2012 (e-pub only)

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