A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma

We reported previously that the addition of recombinant Escherichia coli hu man granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluoro uracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased S-FU dose intensity (J, L. Grem et at, J. Clin, Oncol., 1 2: 560-568, 1994), We then tested the effect of GM-CSF given with a more to xic regimen of 5-FU/LV/ IFN-alpha (IFN alpha-2a), Thirty-one patients with a good performance status and no prior chemotherap y for systemic disease received IFN alpha-2a (5 MU/m(2) s.c., days 1-7), 5- FU (370 mg/m(2) i.v., days 2-6), LV (500 mg/m(2) i.v., days 2-6), and GM-CS F (Saccharomyces cerevisiae 250 mu g/m(2) s.c,, days 7-18) every 3 weeks. T oxicities and 5-FU dose intensity were compared with that observed in our p rior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993), In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity gr ades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxici ty were significantly lower in the present trial, whereas nausea/vomiting a nd fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present tr ial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (4 6%) had stable disease for greater than or equal to 12 weeks. Despite treat ment-related toxicity, patient quality of life did not worsen during the st udy, No correlation was observed between thymidylate synthase content in pr imary tumor specimens and response, time to treatment failure, or survival The addition of GM-CSF appeared to decrease the severity of leukopenia, gra nulocytopenia, mucositis, and skin rash when compared with our prior experi ence with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater naus ea/vomiting and fatigue. The potential impact of increased 5-FU dose intens ity on clinical response, however, remains to be determined.