Clinical observation of Kanglaite Injection combined with EPOCH regimen to treat relapsed or resistant advanced non-hodgkin s lymphoma

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1 Clinical observation of Kanglaite Injection combined with EPOCH regimen to treat relapsed or resistant advanced non-hodgkin s lymphoma 康莱特联合 EPOCH 方案治疗复发或难治性中高度恶性非霍奇金淋巴瘤的临床观察 FU Xiaorui, ZHANG Zijuan, SUN Zhenchang, et al. The First Hospital of Zhengzhou University, Zhengzhou, China [ABSTRACT] Objective: To observe the curative effect and adverse reaction of Kanglaite Injection combined with EPOCH regimen on relapsed or resistant advanced Non-Hodgkin s Lymphoma. Methods: The relapsed or resistant advanced non-hodgkin s Lymphoma patients confirmed by pathological and immuno-histochemical method were randomly divided into two groups, the control group with 25 cases, using EPOCH regimen; the treatment group with 23 cases, chemotherapy with Kanglaite Injection. Results: The effective rate (CR+PR), digestive tract and adverse reaction in blood of the treated group are better than those of the control group, and the difference is significant Conclusion: The combination of KLT with chemotherapy for treating non-hodgkin s' Lymphoma can heighten the curative effect of chemotherapy, reduce toxic and side effects of chemotherapy, improve patient quality of life. Journal of Medical Forum Vol. 31 No. 21 November 2010: Major means to treat non-hodgkin s lymphoma (NHL) remain comprehensive treatment of chemotherapy. Clinical doctors are still beset by therapeutic result of relapsed or resistant advanced NHL cases and various adverse reactions after treatment although there are big improvement in NHL s treatment and its therapeutic result along with progress of medical development. Occurrence, development and prognosis of tumor have close relation with body s immunological status. Patients are, in chemotherapy, associated with immunodeficiency. How to improve patient immuno-function has become an important aspect in tumor treatment study at home and abroad. Kanglaite Injection (KLT) is an anticancer TCM and has notable biphasic function in immunological regulation and antineoplastic synergistic action. A great deal of studies have verified that it has action of toxicity reduction and efficacy enhancement [1-2]. We select 23 cases with relapsed of resistant advanced NHL treated by KLT combined with EPOCH regimen at Oncological Dept. of the first Hospital of Zhengzhou University

2 between October 2006 and October 2009 and 25 cases of relapsed of resistant advanced NHL with pure chemotherapy in control group. Following is the summary. 1. Material and method 1.1 General information 48 patients were pathologically and immono-histochemically confirmed as relapsed or resistant advanced NHL with 32 male and 16 female cases, age years, medium age 53 years (39 cases 60 years, 9 cases >60 years). Middle-malignant group 31 cases, high-malignant group 17 cases; B-cell origin 33 cases, T-cell origin 15 cases; stage II 14 cases, stage III 25 cases, stage IV 9 cases; ECOG 0~1 points 32 cases, 2~3 points 16 cases; IPI 2 in average, LDH higher than normal level in average; bone-marrow invasive 12 cases; spleen invasive 8 cases; 31 recurrence cases (64.6%); never complete remission 17 cases (35.4%). Regimens like CHOP, ECHOP, DICE, MINE, DHAP were once applied and all cases once received CHOP or CHOP-like regimens (ECHOP or BCHOP, etc.). Median number to receive chemotherapy regimen was 4 (2~15). Median accumulated amount was 220 (120~360) mg/m Criteria of enrollment (1) All 48 cases had confirmed pathological and immuno-histochemical diagnosis; (2) With normal heart, hepatic and renal function with peripheral blood WBC count >3.5x10 9 /L and platelet count >100x10 9 /L; (3)ECOG status were 0~3; (4) Estimated survival 3 months; (5) Response rate and adverse reaction were evaluable. 1.3 Treatment method In treatment group protocol of Kanglaite Injection (KLT) combined with EPOCH was adopted: KLT 200ml, iv drip, once/day, d 1~14, 21 days as a cycle. EPOCH regimen: VP-16 50mg/m 2, d 1~4 pump, 24h; VCR 0.4mg/m 2, d 1~4 pump, 24h; ADM 10mg/m 2, d 1~4 pump, 24h; CTX 750mg/m2, d5 iv injection, PDN 60mg/m 2, taken orally, d 1~5 with 21 days as a cycle. Chemotherapy protocol in control group was the same as that in treatment group. 1.4 Criteria of response rate Clinical evaluation was made according to WHO s Evaluation criteria of response rate and adverse reactions i.e. Complete remission (CR), Partial remission (PR), Stable disease (SD) and Progressive disease (PD) with adverse reaction divided into 0-~IV degrees.

3 1.5 Statistical processing SPSS13.0 was applied for analysis and t test was used for comparison between groups with P<0.05 as significant difference. 2. Results 2.1 Short-term response rate Among 23 cases in treatment group, 8 had CR (34.8%), 12 had PR (52.2%), 2 had SD (8.6%) and 1 had PD (4.4%), CP+PR=87.0%. Among 25 cases in control group, 5 had CR (20.0%), 9 had PR (36.0%), 8 had SD (32.0) and 3 had PD (12.0%). CR+PR=56.0%. There was significant difference statistically (P<0.05). See Tab. 1. Tab.1 Short-term response rate between the two groups Group Cases CR PR SD PD CR+PR (%) Treatment Control Note: In RR comparison between the 2 groups, difference had significance P< Adverse reaction Neutropenia in treatment was 43.5% but 92.0% in control group (P<0.05). Anemia in treatment group was 13.0% but 36.0% in control group (P<0.05). Thrombocytopenia in treatment group was 17.4% but 56.0% in control group (P<0.05). Incidence of vomit and nausea was 39.3% in treatment group but 80.1% in control group (P<0.05). See Tab. 2. Tab.2 Comparison of adverse reaction between the two groups Treatment group Control group Adverse Incid- Incid- reaction I II III IV ence % I II III IV ence % Neutro- penia Anemia Thrombocytopenia Vomit & nausea

4 3. Discussion Chemotherapy is major treatment to moderate and high-grade NHL and CHOP remains to be considered as a standard first line regimen with long-term survival of 40% [3]. 60% patients will eventually have recurrence or drug resistance. Traditionally regimen of non-cross resistance like EPOCH is mainly adopted. Compared with traditional rescue regimen, response rate and remission period of EPOCH regimen are higher than other rescue chemotherapeutic protocols [4]. However EPOCH presents apparent digestive, hematological and immunological toxic and adverse reactions in tumor treatment so that patient immunological function is lowered and his life quality is affected. Some patients have to give up the treatment due to intolerance of chemotherapeutic adverse reactions. Morikana et al [5] held that killing tumor cells and protecting body s immune function were equally important. Hence seeking a drug that is synergistic to chemotherapy and can reduce adverse reaction at the same time to improve immune function of human body is an orientation in current tumor treatment. Major ingredient of Kanglaite Injection is coix seed oil. Kanglaite Injection has been proven to have anti-neoplastic and immune function enhancing effect as a new anticancer TCM [6]. Following clinical studies have also verified that Kanglaite Injection, combined with chemotherapy, can notably improve result of chemotherapy, reduce bone-marrow inhibition and digestive adverse reactions like nausea and vomit, improve patient immune function and life quality so that chemotherapy can be tolerated [7]. Data in this study showed that response rate in treatment group was 87.0% and in pure chemotherapy group was 56.0%, P<0.05 with significant statistic difference. This is possibly related to its action to retard cell mitosis, inhibition of cell multiplication, tumor cells apoptosis and also synergy to chemotherapy. In regimens of chemotherapy plus Kanglaite Injection and pure chemotherapy, changes of neutrophilic granulocyte were compared between the two groups before and after the treatment. Neutropenia in treatment group was less severe than that in control group (P<0.05). This showed that addition of Kanglaite Injection could lead to reduction of neutropenia and minimization of secondary infection so that chemotherapy could be completed smoothly. Data from this study also indicated that incidence of toxic and adverse reactions in treatment group was apparently lower than that in control group P<0.05, so that patients immune capacity were elevated, survival quality was improved tolerance to chemotherapy was enhanced to guarantee smooth chemotherapy.

5 This study showed that Kanglaite Injection was quite safe as a TCM anticancer drug. To recurrent and refractory moderate and high-grade malignant NHL, Kanglaite Injection played active role to raise response rate in combination with chemotherapy, to minimize toxic and adverse reactions, to improve patients clinical symptoms and survival quality. Kanglaite Injection is worth to be promoted in clinical application. [References] [1] Qu Jinsong, Yan JIanqiang. Kanglaite Injection in combination with chemotherapy to treat middle stage and advanced non-small-cell lung cancer[j]. Journal of Practical Oncology, 2009, 17(4): [2] Li M, Wang F, Pan XM. Gemcitabine combined with Kanglaite Injection in treatment for 30 cases with elderly advanced non-small cell lung cancer[j]. J Onco, 2009, 15(4): [3] Messori A, Trippoli S, Valan Mi, et al. Survival in patients with intermediate or high grade non-hodgkin's lymphoma: meta-analysis of randomized studies comparing third generation regimens with CHOP[ J]. Br J Cancer, 2001, 84(3): [4] Julie M. Treatment of relapsed aggressive non-hodgkin's lymphomas advances in the management of relapsed aggressive non-hodgkin's lymphoma and Hodgkin's disease abstracts of satellite symposium. 8th International Conference on Malignant Lymphoma[J]. Annals of Oncology, 2002, 13(Sup2): 201. [5] Morikawa K, Hosokawa M, Hamada J, et al. Possible participation of tumor ricidal macrophage in the therapeutic effect of blieomycin on a transplantable rat fibro sacoma[j]. Cancer Res, 1986, 46(2): [6] Liao Guoqin, Wang Guihui, Liu penghui, et al. Clinical observation of Kanglaite Injection in combination with chemotherapy to treat advanced non-small-cell lung cancer[j]. Journal of Practical Oncology, 2009, 24(6): [7] Zhang Juan, Li Qinfeng, Zhou Qinfeng. Observation on impact on Kanglaite Injection on survival quality of advanced cancer patients[j]. Medical Forum, 2009, 30(21):