Concurrent Fludarabine and Total Body Irradiation (F-TBI) for Patients with Advanced Relapsed, Refractory, or Resistant Indolent Non-Hodgkin's Lymphoma (NHL): A Phase I Trial.

Reviewer: William Levin, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 10, 2001

Presenter: David Eilender
Presenter's Affiliation: Wayne State University
Type of Session: Poster

Background

Both chemotherapy (CHT) and radiation therapy (RT) are used in the treatment of non-Hodgkin's lymphoma (NHL).

It is well known that when certain chemotherapeutic agents are given with RT there is a synergistic effect.

The current study investigates the combination of Fludarabine and total body irradiation (TBI) in the treatment of patients with advanced relapsed, refractory, or resistant indolent NHL.

The goal of this Phase I study was to determine the toxicity and maximum tolerated dose (MTD) of F and TBI (F-TBI).

The other aim of the study was to observe the response of F-TBI in patients with relapsed, refractory NHL.

Materials and Methods

Advanced relapsed, refractory, or resistant indolent NHL.
Previously treated, but not post-bone marrow or peripheral stem cell transplant.
Good renal function,absolute neutrophil count and platelet count.
Good perfomance status
Criteria for dose-limiting toxicity (DLT) (any of the following 4:
1. Plts <20x10(9)(ten-to-the-9th) or an ANC <0.5x10(9) for >10 days.
2. Plts not >100x10(9) or ANC not >1.5x10(9) by day 43.
3. If bone marrow >30%, then plts not >50x10(9) or ANC >0.8x10(9) for the first 2 cycles, by day 43.
Maximum tolerated Dose (MTD)
1. Maximum dose level RT, with DLT in <3 of 8 patients.
2. Treat at least 8 patients at the MTD.

Results

20 pts were enrolled from 1998-2001

6 pts were enrolled at the first dose level (F was 25mg/m2/d IV and TBI was 0.1Gy/d given on d1-3 q4-6 wks)

5 pts were enrolled at the second dose level (TBI dose was 0.15 Gy/d), 3 of them did not receive >3 cycles due to prolonged thrombocytopenia.

Since the intent of the study was to give 4-6 cycles of F q4-6 weeks 9 more patients were enrolled at the first TBI dose, the MTD.

DLT was prolonged thrombocytopenia.

Only 1 patient died within 30 days of treatment.
5 pts died of progressive disease.
2 deaths were not evaluable.
3 patients died of infection (not neutropenic).
10 pts are still alive to date.
Author's Conclusions
Toxicity of F-TBI was low compared to other salvage therapies, such as bone marrow transplant.
Aggressive treatment of infections was required.
Clinical/Scientific Implications
This phase I study offers some evidence of efficacy and safety in the treatment of advanced relapsed, refractory, or resistant indolent NHL with F-TBI.
Further studies with increased numbers of patients and longer follow-up are necessary
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