Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma
Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma
In previous studies, the investigators found that in patients with Hodgkin's lymphoma (HL)
 treated with ABVD (adriamycin, bleomycin, vinblastine and decarbazine) the absence of
 alopecia may predict for a poor response to treatment [complete remission (CR) rate 79%
 versus 31%, P < 0.0005, respectively]. Also, patients without alopecia had fewer episodes of
 either leucopenia, neutropenia, deferral of treatment courses or number of courses with dose
 reduction [88% vs. 62.5%, P=0.05, for the presence of at least one of them].

 One of the explanations for this phenomenon is related to a lower systemic exposure of
 chemotherapeutic drugs in patients who retain their hair. There is a wide interpatient
 variability in the pharmacokinetic and pharmacodynamic parameters of doxorubicin systemic
 exposure and the degree of myelosuppression.

 In a pilot study on 18 patients the investigators could not find the previous association
 between alopecia, response to chemotherapy and bone marrow depression. However, when
 analyzing doxorubicin pharmacokinetics, patients who had no remission had 2 fold lower AUC
 (area under the curve) and 3 fold lower peaks (p=0.06). The investigators' lack to approve
 the previous findings might be explained by the small study group.
Aim of the study:

 To evaluate the association between response to chemotherapy, the degree of myelosuppression
 and the pharmacokinetics of doxorubicin in non-Hodgkin's lymphoma (NHL) patients.

 Methods:

 Study protocol:

 1. At diagnosis

 Demographic and clinical parameters be collected (Appendix 1)

 2. At course 2:

 1. Doxorubicin will be given by 5-7 minutes infusion before the other medications
 (Doxorubicin doses will be collected (Appendix 1))

 2. Blood will be sampled in course 2, at:

 0 minutes 30 minutes 120 minutes 24 hours

 Two 2ml EDT tubes will be drawn at each time The tubes will be centrifuged at 3000 RPM for 15
 min. Plasma samples will be stored in - 700C

 3. At the end of chemotherapy courses the following data will be collected (Appendix 2):

 1. Episodes of bone marrow depression (leucopenia, neutropenia) Treatment delays Dose
 reductions Neutropenic fever

 2. Remission status

 [Complete remission (CR) - disappearance of clinical signs and symptoms of NHL along with
 normal laboratory and radiological findings].

 4. At the end of one year of CR

 Remission status

 Number of patients: 30
Inclusion Criteria:

 -  Age ≥ 18 years

 -  Biopsy proven intermediate grade NHL

 -  No previous chemotherapy

 -  At least 4 courses of R-CHOP at maximal doses are planned

 -  An informed consent

 Exclusion Criteria:

 -  Do not meet all inclusion criteria