Lonsurf Adverse Reactions

The following clinically significant adverse reactions are discussed in Precautions: Severe Myelosuppression.
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data in Precautions and as follows reflect exposure to Lonsurf at the recommended dose in 533 patients with metastatic colorectal cancer in the RECOURSE study and 335 patients with metastatic gastric cancer in the TAGS study. Among the 868 patients who received Lonsurf, 11% were exposed for 6 months or longer and 1% were exposed for 12 months or longer. The most common adverse reactions or laboratory abnormalities (≥10%) are anemia, neutropenia, fatigue/asthenia, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting and pyrexia.
Metastatic Colorectal Cancer: The safety of Lonsurf was evaluated in the RECOURSE study, a randomized (2:1), double-blind, placebo-controlled trial in patients with previously treated metastatic colorectal cancer [see Pharmacology: Pharmacodynamics: Clinical Studies: Metastatic Colorectal Cancer under Actions]. Patients received Lonsurf 35 mg/m²/dose (n=533) or placebo (n=265) twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. In the RECOURSE study, 12% of patients received Lonsurf for more than 6 months and 1% of patients received Lonsurf for more than 1 year.
The study population characteristics were: median age 63 years; 61% male; 57% White, 35% Asian, and 1% Black.
The most common adverse drug reactions or laboratory abnormalities (≥10% in incidence) in patients treated with Lonsurf at a rate that exceeds the rate in patients receiving placebo were anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia.
In the RECOURSE study, 3.6% of patients discontinued Lonsurf for an adverse reaction and 14% of patients required a dose reduction. The most common adverse reactions or laboratory abnormalities leading to dose reduction were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.
Tables 5 and 6 list the adverse reactions and laboratory abnormalities (graded using CTCAE v4.03), respectively, observed in the RECOURSE study. (See Tables 5 and 6.)

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In the RECOURSE study, pulmonary emboli occurred more frequently in Lonsurf-treated patients (2%) compared to no patients on placebo.
Metastatic Gastric Cancer: The safety of Lonsurf was evaluated in the TAGS study, an international, randomized (2:1), double-blind, placebo-controlled trial in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who were previously treated with at least 2 prior chemotherapy regimens for advanced disease [see Pharmacology: Pharmacodynamics: Clinical Studies: Metastatic Gastric Cancer under Actions]. Previous treatments must have included a fluoropyrimidine, a platinum, and either a taxane or irinotecan. Patients with HER2/neu-positive tumors must have received prior HER2/neu-targeted therapy, if available. Adjuvant chemotherapy could be counted as one prior regimen in patients who had recurrence during or within 6 months of completion of the adjuvant chemotherapy. Patients received Lonsurf 35 mg/m²/dose (n=335) or placebo (n=168) twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle with best supportive care. In the TAGS study, 10% of patients received Lonsurf for more than 6 months and 0.9% of patients received Lonsurf for more than 1 year.
The study population characteristics were: median age 63 years (24 to 89 years); 73% male; 70% White, 16% Asian, and 1% Black.
The most common adverse reactions or laboratory abnormalities (≥10% in incidence) in patients treated with Lonsurf at a rate that exceeds the rate in patients receiving placebo were neutropenia, anemia, nausea, decreased appetite, thrombocytopenia, vomiting and diarrhea.
In the TAGS study, 13% of patients discontinued Lonsurf for an adverse reaction and 11% of patients required a dose reduction. The most common adverse reactions or laboratory abnormalities leading to dose reduction were neutropenia, anemia, febrile neutropenia, and diarrhea.
Tables 7 and 8 list the adverse reactions and laboratory abnormalities (graded using CTCAE v4.03), respectively, observed in TAGS. (See Tables 7 and 8.)

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In the TAGS study, pulmonary emboli occurred more frequently in Lonsurf-treated patients (3.1%) compared to 1.8% for patients on placebo.
Additional Clinical Experience: Interstitial lung disease was reported in 15 (0.2%) patients, 3 of which were fatal, among approximately 7,000 patients exposed to Lonsurf in clinical studies and clinical practice settings in Asia.