Cancer Res Treat.  2017 Oct;49(4):1022-1032. 10.4143/crt.2016.495.

Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost–Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study

• Woo SM
• Kim MK
• Joo J
• Yoon KA
• Park B
• Park SJ
• Han SS
• Lee JH
• Hong EK
• Kim YH
• Moon H
• Kong SY
• Kim TH
• Lee WJ

• KMID: 2394821
• DOI: http://doi.org/10.4143/crt.2016.495

Abstract

PURPOSE
This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.
MATERIALS AND METHODS
In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m²) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m²/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).
RESULTS
Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).
CONCLUSION
Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

Keyword

Pancreatic neoplasms; Radiotherapy; Gemcitabine; Cisplatin

MeSH Terms

Anemia
Cisplatin*
Codon
Compliance
DNA
Feasibility Studies*
Humans
Induction Chemotherapy*
Nausea
Neutropenia
Oncogenes
Pancreatic Neoplasms*
Polymerase Chain Reaction
Radiotherapy*
Vomiting
Cisplatin
Codon
DNA

Figure

• 

  Fig. 1. Treatment schema, showing induction chemotherapy with GEM and cisplatin, followed by GEM-based SIB-IMRT. CBC, complete blood count; EUS, endorectal ultrasound; CT, computed tomography; MRI, magnetic resonance imaging; CA 19-9, carbohydrate antigen 19-9; PET, positron emission tomography; CEA, carcinoembryonic antigen; LFT, liver function test; GEM, gemcitabine; SIB-IMRT, simultaneous integrated boost–intensity modulated radiotherapy; PTV, planning target volume.

• 

  Fig. 2. Flow of patients through the protocol treatment. Gem-Cis, gemcitabine plus cisplatin; SIB-IMRT, simultaneous integrated boost–intensity modulated radiotherapy.

• 

  Fig. 3. Progression-free survival and overall survival of all patients.

• 

  Fig. 4. Cell-free DNA (cfDNA) concentration, KRAS mutant concentration and fractional abundance before an d after treatment.

Reference

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