Initial Treatment for Non-Bulky Hodgkin’s Disease: Lack of Benefit from Combined Modality

Abstract & Commentary

Synopsis: Effective initial treatment for early stage Hodgkin’s disease can include radiation or chemotherapy, or both. In a randomized study conducted at Memorial Sloan Kettering, patients with stage I, II, or IIIA disease (non-bulky) were randomized to receive radiation plus chemotherapy or chemotherapy alone. There were no differences observed in remission rate or duration or overall survival.

Source: Straus DJ, et al. Blood. 2004;104(12):3484-3489.

Several therapeutic regimens have been used in the treatment of early stage Hodgkin’s disease. Between 1975 and 1986, different combinations of chemotherapy were added to the standard treatment of radiation therapy, demonstrating improved clinical outcomes.1,2 Various chemotherapy regimens were investigated with the goal of maintaining the high level of response while reducing toxicity. The question remains, however, whether chemotherapy alone would achieve the high level of clinical response as combined modality therapy (CMT). Straus and associates conducted a single institution (Memorial Sloan Kettering) randomized, prospective study aimed to determine whether differences in outcome are achieved with CMT vs chemotherapy (CT) alone in the treatment of nonbulky Hodgkin’s disease.3 The researchers hypothesized that CMT would be superior to CT in freedom from progression (FFP) and overall survival (OS).

One hundred fifty-two patients with Hodgkin’s disease stages IA, IB, IIA, IIB, or IIIA were randomized to 6 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or ABVD followed by radiation therapy (RT). Of the 65 patients who received RT after ABVD, 94% achieved complete remission (CR) while 6% demonstrated no significant response. The ABVD group achieved 94% CR while 1.5% showed partial response (PR) and 4.5% had no significant response. No overall significant difference was noted between the two groups in CR, PR, FFP and OS (after 60 months CR duration).

Comment by William B. Ershler, MD

This report describes the results from a single institution of a randomized trial of ABVD + radiation therapy vs ABVD alone for the treatment of stage I, II or IIIA non-bulky Hodgkin’s disease. It was conducted over a 10-year period and no significant differences were observed in the relevant clinical parameters of remission rate, duration of remission and overall survival. However, Straus et al noted that at 60 months, overall survival in the combined modality arm was 97% compared to 90% in the chemotherapy alone arm (P = .08) and they speculated that this difference might prove significant in a larger trial.

What is missing in this report, but covered succinctly in the accompanying editorial4 is the weight of evidence of long-term consequences of radiation, particularly the occurrence of second malignancies.5-7 Ng and colleagues5 have estimated the death rate from second malignancies in radiation treated Hodgkin’s patients to be approximately 10% based on a median follow-up of 12 years in patients who were treated before the age of 50 years. Accordingly, it is quite possible that more radiation-treated Hodgkin’s patients will die of complications of therapy than of Hodgkin’s disease, itself.

Thus, the optimal treatment for early stage Hodgkin’s disease, despite decades of available effective approaches, remains controversial. What the Memorial experience has shown is that combined modality does not offer significant advantage for initial treatment of non-bulky disease. Thus, it would seem prudent that such patients be treated initially with combination chemotherapy, and radiation be reserved for those who fail to enter complete remission or who relapse with disease.

William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.

References

1. Koziner B, et al. Cancer. 1984;54:1928-1942.

2. Straus DJ, et al. Cancer. 1992;69:1052-1060.

3. Wiernik PH, et al. Am J Med. 1979;67:183-198.

4. Longo DL. Blood. 2004;104:3418.

5. Swerdlow AJ, et al. J Clin Oncol. 2000;18:498-509.

6. Dores GM, et al. J Clin Oncol. 2002;20:3484-3494.

7. Ng AK, et al. J Clin Oncol. 2002;20:2101-2108.