Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial

Abstract

SummaryBackgroundIn the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer.MethodsIn this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m2 on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m2 twice daily on days 1–21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0–1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m2 once per week) or capecitabine (830 mg/m2 twice daily, Monday to Friday only), both in combination with radiation (50·4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987.Findings114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62·9%, 80% CI 50·6–73·9) in the capecitabine group and 18 of 35 assessable patients (51·4%, 39·4–63·4) in the gemcitabine group had not progressed. Median overall survival was 15·2 months (95% CI 13·9–19·2) in the capecitabine group and 13·4 months (95% CI 11·0–15·7) in the gemcitabine group (adjusted hazard ratio [HR] 0·39, 95% CI 0·18–0·81; p=0·012). 12-month overall survival was 79·2% (95% CI 61·1–89·5) in the capecitabine group and 64·2 (95% CI 46·4–77·5) in the gemcitabine group. Median progression-free survival was 12·0 months (95% CI 10·2–14·6) in the capecitabine group and 10·4 months (95% CI 8·9–12·5) in the gemcitabine group (adjusted HR 0·60, 95% CI 0·32–1·12; p=0·11). Eight patients in the capecitabine group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had grade 3–4 haematological toxic effects (seven [18%] vs none, p=0·008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0·12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia, and fatigue. Two patients in the capecitabine group progressed during the fourth cycle of induction ch...

Advances in Chemotherapy for Pancreatic Cancer

“…There is no consensus on the superiority of chemotherapy versus chemoradiotherapy from the available information, with reports of increased toxicity especially with Gemcitabine with the use of chemoradiotherapy in the reported trials. [52] Retrospective series have reported improved outcomes with median survival favouring chemoradiotherapy over chemotherapy (15 vs. 11.7 months) [53] Similar results were reported by the Eastern Cooperative Oncology Group 4,201 study [54] with Gemcitabine and chemoirradiotherapy with Gemcitabine showing chemoradiotherapy was associated with significantly improved median survival from 9.2 months in the chemotherapy alone arm to 11.1 months .…”

“…For patients with localized disease who have difficulty tolerating chemotherapy, patients experiencing symptoms from their primary tumour, or patients who may be considered for surgical exploration, consolidative chemoradiotherapy to optimize local tumour control and surgical resectability may be explored. Table 3 shows some studies of chemotherapy versus chemoradiotherapy in patients with LAPC [52,54,[56][57][58][59].…”

The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

“…Data from prospective trials containing patients with borderline resectable disease demonstrate that the surgical resection rate ranges from 24 to 64%, and the R0 resection rate ranges from 87 to 100% [56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Although most of these studies are small, neoadjuvant chemoradiation appears to be associated with good potential for downstaging and R0 resection in this population, which may be in part due to careful patient selection with adequate staging studies, and strict adherence to the definition of borderline resectable.…”

“…Neoadjuvant therapy with the intent of sterilizing the margin could be considered in patients with vascular involvement, with particular attention to restaging to tailor surgical recommendations. Several studies suggest that neoadjuvant chemoradiation may enhance margin-negative resectability rates and improve local control [37,[56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Unfortunately, many of the studies are confounded by inclusion of patients with locally advanced unresectable tumors and lack of strict definition of borderline resectable disease.…”

Место Адъювантной Лучевой Терапии При Раке Поджелудочной Железы – В Клинических Исследованиях

“…При этом сроки ее начала не должны превышать 12 недель после операции, а общая длительность должна составлять 6 месяцев. Добавление лучевой терапии во время химиотерапии приводит к зна-чительному снижению интенсивности дозы химиотерапии [15], что также нежелательно ввиду наличия доказательств, что это снижение дозы влияет на прогноз пациентов.…”