The treatment of locally advanced pancreatic cancer: RESULTS (Part 2)

In: Pancreatic cancer

17 Jul 2012

Chemoradiotherapy versus radiotherapy alone: Two randomized trials evaluated combined-modality therapy compared with radiotherapy alone (Table 1[A]). The first trial was published by Moertel et al in 1969, and it included patients with locally advanced stomach, colon and pancreatic cancer. Radiation was given as six fractions per week, with a weekly dose of nine to 12 Gray (Gy), to a total dose of 35 to 40 Gy. Patients who were randomly assigned to chemotherapy received 5-FU 45 mg/kg daily for the first three days of radiation.

Toxicity, in the form of nausea, vomiting, diarrhea and marrow suppression, was more frequent with chemoradiotherapy than with radiotherapy alone, but it was described as tolerable. No deaths were ascribed to therapy. The addition of chemotherapy to radiation significantly increased survival for patients with all three tumour types. For patients with locally advanced pancreatic cancer, the mean survival time was significantly increased from 6.3 to 10.4 months when 5-FU was added to radiotherapy (P<0.05). The median survival, as estimated from the published survival curves, was increased from approximately 5.6 months to 8.0 months.

TABLE 1 Randomized trials in locally advanced pancreatic cancer

Reference Radiation(Gy) Chemotherapy Number of patients randomized (evaluable) Median Survival (months) Percentage one-year survival (estimate*)
A) Chemoradiotherapy versus radiotherapy alone
Moertel et al, 35-40 5-FU NR (32) 10.4t NR (25t)
1969 35-40 Placebo NR (32) 6.3 NR (6)
GITSG 9273, 60 5-FU 111 (86) 11.4 44t
1981  40 5-FU 117 (83) 8.4 39t
60 25 (25) 5.3 14

 *Calculated from survival curve where data not provided in the text; Tp<0.05. 5-FU Bolus 5-fluorouracil; ECOG Eastern Cooperative Oncology Group; GITSG Gastrointestinal Tumor Study Group; Gy Gray; mCCNU Methyl lomustine; NR Not reported; RTOG; Radiation Therapy Oncology Group; SMF Streptozocin, mitomycin, 5-FU; SWOG Southwest Oncology Group

The Gastrointestinal Tumour Study Group (GITSG) undertook a three-arm study of 60 Gy double-split radiotherapy with two, two-week rest periods compared with the same radiation dose combined with 5-FU, or 40 Gy single-split course with 5-FU (Table 1[A]). In the chemotherapy-containing arms, 5-FU was given at a dose of 500 mg/m2 intravenously (IV) on the first three days of each 20 Gy of radiation, and then continued as a weekly bolus infusion for two years. The radiation-alone arm was stopped after only 25 patients had been enrolled because it had become clear that both the median survival time and the one-year survival rate were half those in the chemotherapy-containing arms (P<0.01). There was no significant survival difference between the two combined-modality arms, although there was a nonsignificant trend toward prolonged time to progression (P=0.14) and improved survival (P=0.19) for 60 Gy over 40 Gy, suggesting a dose-response relationship. However, the nonstatistically significant advantage for the 60 Gy over the 40 Gy arm did not result in longer term survival as evidenced by the survival curves overlapping at 15 months. Local failure was a component of progression in about 25% of patients. Toxicity mostly consisted of nausea/vomiting and leucopenia, which occurred in all groups. Severe toxicity (up to 5% of patients) and mucositis occurred only in patients receiving 5-FU.

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