Korean Journal of Medicine

Transcription

1 Vol. 57, Suppl. II October, 1999 ISSN X Korean Journal of Medicine 51th Meeting The Korean Association of Internal Medicine Fall Meeting Oral Presentation and Poster Section October 22-23, 1999 Sheraton Walker-Hill Hotel Kim, M.: Korean Journal Med / 9

2 Comparative Study on the Effects of a Viscum album (L.) Extract (Mistletoe) and Doxycycline for Pleurodesis in Patients with Malignant Pleural Effusion Myung-hoon Kim, M.D., Yong-keun Park, M.D., Sang-hak Lee, M.D., Suk-chan Kim, M.D., Sook-young Lee, M.D., Chi-hyeung Kim, M.D., Young-kyun Kim, M.D., Kwan-hyung Kim, M.D., Hwa-shik Moon, M.D., Jung-sup Song, M.D., and Sung-hak Park, M.D. Department of Internal Medicine, College of Medicine, Catholic University, Seoul, Korea Translated from Korean Journal of Medicine, 57:S121, Suppl. II (1999) ABSTRACT Background: Conventional agents to achieve pleurodesis to manage malignant pleural effusion often caused patients severe side effects such as pain and burning sensation. Previous studies showed that Helixor manifested less side effects when used as a pleurodesis agent in patients with malignant pleural effusion, while it potentiates immune functions against the cancer cells. In this study, we conducted a prospective clinical trial to investigate the therapeutic efficacy and safety of Helixor as compared with those of Doxycycline. Methods: The thirty patients (15 males and 15 females; mean age 55 years, range 22-76) with the diagnosis of malignant pleural effusion were randomly allocated either to receive intrapleural instillation of Helixor or Doxycycline to effect pleurodesis (N = 15 for each group). Therapeutic effects were evaluated clinically as well as by a radiological assessment of pleural effusion. To examine the adverse effects of treatments, pain, burning sensation, and fever (0 not observed, 1 observed; maximal summed score = 3) were evaluated to obtain the index of side effects in patients treated with Helixor or Doxycycline, respectively. Additionally, base-line counts of CD4+ and CD8+ lymphocytes and natural killer (NK) cells were compared with those measured after treatment, to assess the effects of treatment on immune functions. Kim, M.: Korean Journal Med / 9

3 Results: 1) Among the thirty patients with the diagnosis of malignant pleural effusion, primary cancers were identified as follows: lung cancer 23 patients, breast cancer 4, cancer of uterine cervix 1, stomach cancer 1, and unknown primary cancer 1 2) Of the 15 patients treated with Helixor, 11 patients were available for follow-up study, among whom 9 showed complete response, 1 partial response, and 1 no response. Of the 15 patients treated with Doxycycline and available for follow-up study, the number of patients with complete response, partial response and no response were 6, 4, and 5, respectively. Comparison of the number of patients with either complete or partial response with that with no response showed that pleurodesis effect was superior among Helixor group as compared with Doxycycline group (p<0.05; Table 1). 3) With the pleural instillation of Helixor, 6 patients experienced pain and 3 patients fever as adverse events, while burning sensation was not experienced by any patient. In Doxycycline group, 14 patients reported pain, 5 burning sensation, and 6 fever. Mean index of side effects were and in Helixor and Doxycycline groups, respectively, which indicated that adverse events were less severe in Helixor-treated patients. The above difference of side-effect index between 2 groups were statistically significant (p<0.05; Table 2). Base-line counts of CD4+ lymphocytes, CD8+ lymphocytes, and natural killer cells in pleural aspiration fluid were similar between 2 study groups. Significant differences of these parameters of immune functions were not observed following the treatment between Helixor and Doxycycline groups. Although a slight decrease of CD4+ and CD8+ lymphocytes was observed in Helixor-treated patients ( and , respectively, before treatment; and , respectively, after treatment; the difference was not statistically significant. Conclusions: As a pleurodesis agent for the management of malignant pleural effusion, Helixor manifested higher therapeutic efficacy and better safety features as compared with Doxycycline. Further studies are needed to clearly elucidate immuno-modulatory effects of Helixor. Table 1. Pleurodesis effect of Helixor and Doxycycline treatment Kim, M.: Korean Journal Med / 9

4 Helixor (n = 11) Doxycycline (n = 15) Complete response 9 (81%) 6 (40%) Partial response 1 (9%) 4 (26%) No response 1 (9%) 5 (33%) Table 2. Side Effects of Helixor and Doxycycline treatment Side Effect Helixor Doxycycline Pain 6 14 Burning sensation 0 5 Fever 3 6 Side-effect Index Kim, M.: Korean Journal Med / 9

5 Comparative Study on the Effects of a Viscum album (L.) Extract (Mistletoe) and Doxycycline for Pleurodesis in Patients with Malignant Pleural Effusion Myung-hoon Kim, M.D.*, Sang-hak Lee, M.D., Suk-chan Kim, M.D., Young-kyun Kim, M.D., and Sung-hak Park, M.D. Department of Internal Medicine, College of Medicine, Catholic University BACKGROUND Doxycycline has been often used to effect pleurodesis for the management of malignant pleural effusion. However, its use has been limited due to severe side effects and low therapeutic efficacy. Helixor (Mistletoe) is an injection solution extracted from Viscum album L., which is a semi-parasitic plant growing on different host trees. Previous studies showed that Helixor had immuno-modulatory effects by increasing the number of natural killer cells (NK-cells) and might be effective to cause pleurodesis in patients with malignant pleural effusion. STUDY OBJECTIVE Comparison of the therapeutic efficacy and safety of Helixor and Doxycycline as a pleurodesis agent Immunological effect of Helixor treatment on the number of NK cells in pleural aspiration fluid. Kim, M.: Korean Journal Med / 9

6 METHOD I Prospective, Open-label, Randomized, Controlled, Comparative Trial Inclusion Criteria Patients with malignant pleural effusion Patients between 18 and 75 years of age Patients with Karnofsky index 60% Patients without renal, hepatic or bone marrow failures A total of 33 patients were included in the study, who were diagnosed of malignant pleural effusion as confirmed by a pleural biopsy or cytological study of pleural aspiration fluid. Sex: 17 males and 16 females Average age: 54.8 years (range, years) METHOD II Pleurodesis was performed following the random allocation of patients to treatment with either Helixor or Doxycycline. Helixor was initially administered by pleural instillation at a daily dose of 100 mg, which was incremented by 100 mg per day until the daily volume of pleural drainage became less than 100 ml or the daily dosage reached 500 mg. Doxycycline was administered by pleural instillation at a dose of 500 mg and repeated again after one week if the daily volume of pleural drainage remained higher than 100 ml. The 50 mg of Demerol (intramuscular injection) was given as a pretreatment drug before the administration of Doxycycline and lidocaine was concomitantly at a dose of 2 mg/kg with Doxycycline Kim, M.: Korean Journal Med / 9

7 METHOD III The effect of pleurodesis was evaluated by a follow-up study with X-ray images after the administration of the last dose and categorized as follows: Complete Response: no pleural effusion and symptoms Partial Response: Despite the remaining pleural effusion, pleural tapping is not required without any accompanying subjective symptoms. No Response: increased volume of pleural effusion METHOD IV Adverse events were evaluated by assessing 3 most-common side effects, pain, burning sensation, and fever (0 not observed, 1 observed; maximal summed score = 3) to obtain the index of adverse events. The indices of adverse events were compared between 2 study groups following the treatment. Results I: Demographic Characteristics Among Helixor group, follow-up study was done in 13 patients. 6 males and 7 females average age: 61.8 years Among Doxycycline group, follow-up study was done in 16 patients. 8 males and 8 females average age: 50.3 years Kim, M.: Korean Journal Med / 9

8 Results II: Primary Cancer Primary Cancer Cases (total n = 33) Lung cancer 23 Breast cancer 5 Others: Stomach cancer 1 Rectal cancer 1 Uterine cervix cancer 1 Bartholin adenocarcinoma 1 MUO 1 Results III: Responses to Treatments Results IV: Response Rate and Adverse Events Response Rate, Index of Adverse Events Results V: Number of NK Cells SUMMARY In Helixor group, number of patients with CR, PR, and NR was 11, 1, and 1, respectively, and in Doxycycline group, 7, 4, and 5, respectively. Response rates were 95% and 68% in Helixor and Doxycycline groups, respectively, where response was defined as CR and PR combined. In Helixor group, numbers of patients manifesting side effects of pain, burning sensation, and fever were 6, 0, and 3, respectively (mean index of adverse events = ), and in Doxycycline group, 14, 5, and 6, respectively (mean index of adverse events = ). The overall response rates. Following the Helixor treatment, the increase in the number of NK cells was observed. However, the increase was not significant statistically. Kim, M.: Korean Journal Med / 9

9 CONCLUSION Helixor manifested higher therapeutic efficacy and better safety features as a pleurodesis agent for management of malignant pleural effusion as compared with Doxycycline. Kim, M.: Korean Journal Med / 9