Association Between Proton Pump Inhibitors and Hematologic Toxicity of Pemetrexed

Prospective, longitudinal, multicenter and observational study. All eligible patients will receive clear information about aims and research modalities on the medical consultation and before first course of chemotherapy. If patient agrees with study aims and protocol, disease and therapeutic management will not be change.

Research agree and participation leads to

Data collection:

• Clinical data: weight, height, body mass index

  1. Demographic data: sociodemographic data, comorbidities
  2. Disease data: related to tumor disease and antineoplastic protocol including adjuvant medications like antiemetic of antidiarrheal agents for example.
• complete medication review: a minimum of 3 information sources among the patient and/or family and close, patient health records, community pharmacy, general practitioner,
• activation of a specific study patient record
• biologic data collection: blood count and thrombocythemia during all period study and three week after patient study completion,
• supplementary data in case of hematologic toxicity: hospitalization, growth factors (like erythropoietin and/or granulocyte colony-stimulating factor use), blood transfusions, intravenous iron, chemotherapy treatment delay All patients are followed since inclusion and for 18 months. Research logistic Patients will be recruited in cancer hospital service where patients received pemetrexed in the four study participant centers. Full information and all necessary clarification about study will be explained to all eligible patients with an appropriate consent form. Data collection using case report form will be performed by pharmacists and physicians from hospitalization setting.

Recruiting duration period Twelve months

Subject duration period Eighteen months Subject accessibility Patients will be recruited in one of the four participant centers Statistical analysis Number of patients to include with statistical considerations

It is planned to include 100 patients per group after calculating the number of subjects required (nQuery software) taking into account the following assumptions:

• Risk alpha = 0.05
• Statistical power = 90%
• Percentage of patients without hematologic toxicity in PPI-negative group = 0.62
• Percentage of patients without hematologic toxicity in PPI-positive group = 0.88 (Hazard ratio = 3.74) Statistical analysis methods of criteria Data description will be performed using mean and standard deviation or median (interquartile interval and minimum and maximum) for quantitative variables according to variable distribution and number and percentage for qualitative variables.

Bivariate analysis will be conducted in order to found the association between hematological toxicity or not and clinical variables. Multivariate analysis will be performed with Cox model, using a dependent variable "presence or not of a hematologic toxicity" and independents variables, variables that are associated with a "p" less than 0.20 with confusion factors adjustment.

Treatment of missing data The study will be performed in order to minimize the number of missing data. For each variable number and percentage of missing data will be described.