Abstract
Dear Editor:
Bortezomib has contributed to the remarkable advancement of the treatment of patients with multiple myeloma (MM). The common side-effects of bortezomib are peripheral neuropathy, thrombocytopenia, weakness, and gastrointestinal toxicity. Recently, an increased incidence of varicella zoster virus (VZV) reactivation (herpes zoster) was reported in patients with MM undergoing treatment with bortezomib. 1,2 Based on these observations, VZV prophylaxis was recommended in subsequent clinical trials, and the incidence decreased markedly after acyclovir prophylaxis was administered. 1,3,4 Dasanu et al. state that the use of long-term acyclovir prophylaxis could cause significant renal and neurological toxicity. 5
Traditional herbal medicines have been used for a long time in the treatment of human infectious diseases in many countries, and some of them are reported to exhibit antiviral activity in the literature. Traditional Chinese Medicine (TCM) commands a unique position among all traditional medicines because of its 5000 years of history. The Chinese medicinal herb Radix Isatidis has been suggested to possess antiviral activity, and it has fewer side-effects.
From January 2009 to October 2010, the authors evaluated the efficacy of VZV prophylaxis with Radix Isatidis in 30 patients with MM treated with a bortezomib-based regimen. The median age of the patients was 63 years (range, 42–76 years). The median number of administered cycles of bortezomib per patient was 2 (range, 2–4 cycles). Baseline characteristics of the patient cohort are shown in Table 1. Bortezomib was used alone or combined with other drugs such as dexamethasone and thalidomide. Bortezomib 1.3 mg/m2 was administered at days 1, 4, 8, and 11 of each 21-day cycle. Dose reductions or treatment delays were allowed if adverse effects occurred. Patients discontinued treatment if they had progressive disease, developed unacceptable toxicity, withdrew consent, or maintained a confirmed complete response for 2 cycles. 6 The first 12 patients did not receive any VZV prophylaxis. Because of the high incidence of herpes zoster, it was decided to use Radix Isatidis 10 g orally 3 times daily in the subsequent 18 patients. All statistical analyses were performed using a statistical software package (SPSS; Version 13.0).
IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M; VZV, varicella zoster virus.
Of the 12 patients who did not receive any antiviral prophylaxis during bortezomib treatment, 3 patients (25%) developed herpes zoster. The median time to onset of herpes zoster was 24 days. One (1) patient had previous VZV infection. One (1) patient developed a typical rash with blisters on part of his face; the 2 other patients had a rash on their neck or trunk, respectively. All 3 patients applied acyclovir ointment in the affected area and Radix Isatidis 10 g orally 3 times daily. The skin lesions were resolved without any complications in the patients. The subsequent 18 patients treated with bortezomib received VZV prophylaxis with Radix Isatidis. During the period of observation, no cases of VZV reactivation occurred. The incidence of VZV reactivations in patients without VZV prophylaxis was significantly higher than that in patients treated with Radix Isatidis (p=0.003). A multivariate analysis did not show an association between risk of herpes zoster and Karnofsky Performance Scale, prior history of VZV, baseline levels of β2 microglobulin, hemoglobin, or albumin. No adverse effects were noted that could be definitely attributed to Radix Isatidis.
As bortezomib has been shown highly effective in the treatment of MM through changing the response rates and the general prognosis of patients, herpes zoster has been more frequently observed. To the authors' knowledge, the reason for this is not fully understood. Herpes zoster is the result of reactivation of latent VZV from the dorsal root ganglion. Cell-mediated immunity plays a major role in the prevention of development of herpes zoster. With these recent developments, antiviral prophylaxis seems to be increasingly important in ameliorating the risk of VZV reactivation in patients receiving bortezomib-based therapies.
Traditional medicines contain various metabolites derived from nucleic acid, protein, and lipid metabolism. Some of these specific metabolites may recognize the differences between viral and host metabolism resulting in antiviral activity; hence traditional medicines may be useful sources for new antiviral agents. TCM is considered a complementary or alternative medical system in most Western countries while remaining as a form of primary care throughout most Asian countries. In China, Chinese medicine accounts for 30%–50% of total medicine consumption, with low costs and low toxicity. 7 Many TCMs and related active compounds have been reported that have promising and potent antivirus activities. 8
Radix Isatidis (Banlangen in Chinese) is a TCM herb, and is officially recorded in the Chinese Pharmacopoeia. As a medicinal herb, it has been used for more than 2000 years. Radix Isatidis, the root of woad, is traditionally used as an antiviral, antibacterial, anti-endotoxic, and immune regulatory agent in the folk medicine of China. The roots are harvested during the autumn and are dried. The dried root is then processed into granules, which are most commonly consumed dissolved in hot water or tea. The product, called Banlangen Keli, is very popular throughout China and it has fewer side-effects. In China, a few clinical reports showed that the use of large doses or long-term Banlangen granules could cause gastrointestinal toxicity and allergic reactions.
The present study showed that the incidence of VZV reactivations in patients without VZV prophylaxis was significantly higher than that in patients treated with Radix Isatidis. Thus, the drinking of the Radix Isatidis, in a daily tea or coffee, may be used for prophylaxis of and therapy for herpes virus infection during bortezomib treatment and can improve the quality of life in patients with MM. Further clinical trials should be done in the future.
Footnotes
Disclosure Statement
None of the authors declare personal or financial conflicts of interest.