Abstract Objective To compare temozolomide (TMZ) and lomustine (CCNU) in the treatment of glioma efficacy, survival and adverse reactions. Methods 64 patients after the first surgery in patients with glioma were randomly divided into the TMZ groups and CCNU group of 32 cases, the two groups of patients first treated with conventional radiotherapy, 2Gy / d, 5d / W, lasted 4 ~~ 6W-ray total dose 50 ~ 60Gy. One week after the end of radiotherapy, chemotherapy. TMZ group oral TMZ (0.015 to 0.02) mg / (cm2 · d) the 5d / W, every five days for a course of treatment, each treatment interval of 23 days, 28 days for a treatment cycles administered according to patient tolerance 3 to 5 cycles. CCNU group oral CCNU (0.005 to 0.006) mg / (cm2 · d), 5d / w, treatments and treatment cycle with TMZ group. Results TMZ group efficacy significantly better than the CCNU groups (U = 1.9675, P = 0.0245); TMZ group average survival period (14.5 ± 2.5) months, significantly higher than CCNU group (10.5 ± 1.5) months (t = 7.7611, P = 0.000 ); Group TMZ nausea, vomiting, fatigue was significantly lower than CCNU group (χ 2 = 4.0635, P = 0.0437); TMZ group was significantly lower than the degree of bone marrow suppression the CCNU groups (U = 3.2314, P = 0.0006). Conclusion TMZ CCNU significantly reduced tumor volume, to prolong the survival of patients, with few side effects, and improve the patient’s quality of life, is worthy of clinical application.

Key words glioma; temozolomide; lomustine

 Clinical Observation of Temozolomide and Lomustine in Treating with Gliomas

    DENG Yan  nong

    Department of Oncology, Laibin People, s Hospital of Guangxi, Laibin 546100, ChinaAbstract: Objective To compare the therapeutic effect, survival and safety of temozolomide (TMZ) and lomustine (CCNU) on glioma.Methods A total of 64 postoperative patients with glioma were randomly divided into two groups: TMZ treatment and CCNU treatment group.All patients were performed conventional radiotherapy, 2Gy / d, 5d / W, 4 ~ 6 weeks as a treatment course, for a total of 50 ~ 60Gy. After radiotherapy, TMZ group were treated with TMZ (0.015 ~ 0.02) mg / (cm2 · d) by orally for 5 days during 28  day cycle.CCNU group were treated with CCNU (0.005 ~ 0.006) mg / (cm2 · d) by orally for 5 days during 28  day cycle. Results The effect in TMZ group were superior to CCNU group (U = 1.9675, P = 0.0245); the average survival time of patients in TMZ group were longer than that of in CCNU group (t = 7.7611, P = 0.000); the happening rate of nausea, vomitting and tired in TMZ group was lower than that in CCNU group (χ2 = 4.0635, P = 0.0437); The myelotoxicity in TMZ group were slighter than that in CCNU group (U = 3.2314, P = 0.0006). Conclusion TMZ can improve the patients with gliomas in the symptoms and survival quality better, and produce higher response rate compared to CCNU in patients with gliomas.

    Key words: Glioma; Temozolomide (TMZ); Lomustine (CCNU)

Glioma is the most common malignant tumors of the nervous system, has the characteristics of high recurrence rate and high mortality [1]. Clinical generally treated by surgery supplemented by radiotherapy, chemotherapy, immune and gene therapy treatment, but the treatment is poor, with an average survival time of only 36 to 48 weeks within two years, the survival rate of only 8% to 12% [2]. Our hospital from January 2005 to June 2007, observed the effect of of glioma postoperative chemotherapy with temozolomide (temozolomide, TMZ), and the efficacy of control and lomustine (lomustine, CCNU), are as follows.

    1 Materials and Methods

    1.1 Case inclusion criteria

    (1) pathologically confirmed grade Ⅱ ~ Ⅳ anaplastic astrocytoma or pleomorphic glioblastoma; (2) tumor specimens methylguanine methyl transferase (MGMT) were negative; ( 3) voluntary patients for postoperative radiotherapy and chemotherapy; (4) card’s quality of life score [3] (Karnofsky the Performance Scale, KPS) ≥ 60 points; (5) the routine blood examination was normal: hemoglobin (HB) ≥ 100G / L, white blood cell (WBC) ≥ 4.0 × 109 / L, platelet (PLT) ≥ 100 x 109 / L; (6) liver and kidney function is normal. Rule out pregnancy or breast-feeding women, nitrosourea alkylating agent allergy, and patients with serious systemic disease or with active infections. This group of selected patients with a total of 64 cases were randomly divided into two groups (TMZ) and control group (CCNU group) 32 cases each, the TMZ group 20 males and 12 females; aged 26 to 65 years of age, the average (49.5 ± 1.5 years); tumor subtotal resection in 26 cases and partially in six cases. CCNU group of 18 males, 14 females; aged 25 to 64 years old, on average (50.5 ± 2.5) years; tumor subtotal resection in 25 cases, partial resection of the seven cases. The two groups of patients with gender, age, tumor resection extent compare the difference was not statistically significant (P> 0.05), comparable.

    1.2 Treatment

    The patients were in rows 15 to 20 days after conventional radiotherapy, 2Gy / d, 5d / W, lasted 5 ~~ 6W-ray total dose of 50 Gy to 60 Gy was aimed at. One week after the end of radiotherapy, chemotherapy. TMZ group: oral TMZ (Tianjin Tasly Company) (0.015 ~ 0.02) mg / (cm2 · d), 5d / W, a course of five days, each treatment interval of 23 days, 28 days for a treatment cycle, 3 to 5 cycles (at least three cycles) administered according to patient tolerance. The CCNU groups: oral CCNU (0.005 to 0.006) mg / (cm2 · d), 5d / w, treatments and treatment cycles with TMZ group.

    1.3 OUTCOME MEASURES

    (1) efficacy: according to WHO criteria [3] judgment, complete remission (CR): The lesions were completely gone and maintained for at least four weeks or more; partial remission (PR): tumor lesion volume is reduced by 50%; stable (SD): tumor lesions shrinkage ≥ 25%, but less than 50% and no new lesions; disease progression (PD): increased tumor volume ≥ 25%, or new lesions. Seven days before the start of chemotherapy cranial enhanced CT or MR enhanced MRI understand residual of intracranial tumors, every 1 month after the start of chemotherapy, CT or MR enhanced check the change in the volume of the tumors was observed, it is judged and recorded two groups. Efficiency = (CR + PR) / total number of cases × 100%. (2) survival time: two groups of patients were followed up for at least one year, recording its lifetime. (3) adverse reactions. The start of chemotherapy patients with gastrointestinal reactions and fatigue were observed daily, weekly review of liver and kidney function and blood count, and record the changes of the two groups of patients with WBC and PLT. Myelosuppression observed according to the WHO classification [4] into 0 ~ Ⅳ degrees, 0 degrees: WBC ≥ 4.0 × 109 / L, PLT ≥ 100 × 109 / L; Ⅰ degree: WBC 3.0 to 3.9 × 109 / L, PLT 75 ~~ 99 × 109 / L; Ⅱ degree: WBC 2.0 to 2.9 × 109 / L, PLT 50 to 74 × 109 / L; Ⅲ degree: WBC 1.0 to 1.9 × 109 / L, PLT 25 to 49 × 109 / L; Ⅳ degree: WBC <1.0 x 109 / L, PLT <25 x 109 / L,.

    1.4 statistical methods

    SPSS 10.0 software for data processing, counting to compare data between groups using χ2 test, measurement data groups were compared using the t test, rank sum test was used to compare the level data group, P <0.05 for the difference was statistically significant.

    2 Results

    2.1 Comparison of two groups are shown in Table 1. Table 1 Comparison of the efficacy comparison by rank and test: U = 1.9675; P = 0.02452.2 two sets survival time comparison

    TMZ group 10 patients died during the follow-up period (31.3%), the average survival time (14.5 ± 2.5) months; CCNU group of death in 15 cases (46.9%), the average survival time (10.5 ± 1.5) months. The mean survival of the difference was statistically significant (t = 7.7611, P = 0.000).

    2.3 Adverse reactions

    The TMZ group there have been 10 cases (31.3%) patients with nausea, vomiting and fatigue phenomena CCNU group and 18 patients (56.3%), the difference was statistically significant (χ 2 = 4.0635, P = 0.0437). None of the two groups of patients with chemotherapy-related liver and kidney dysfunction, but varying degrees of bone marrow suppression (can be restored within a certain period of time, no long-term bone marrow suppression occurred), as shown in Table 2. Table 2 groups comparing the degree of bone marrow suppression

3 Discussion

    Glioma cell biology and pathology characteristics showed that tumor cells in the brain tissue showed infiltrative growth boundaries is unclear, the surgery is difficult to completely remove with normal brain tissue. Only resection endoscopic surgical microscope to see the local tumor, subclinical lesions can not all resection, recurrence risks will naturally leave. The radiotherapy individuals can only accept a certain dose of radiation, impossible repeated exposure, nor be able to total body irradiation. Therefore looking for a low or no toxicity of anti-glioma drug to extend the survival of patients, and improve the patient’s quality of life, indeed clinically necessary and imperative. TMZ is a new imidazol-tetrazine derivatives of anticancer drugs, and adapted to the acidic environment of the stomach, the food has little influence, the oral bioavailability of 98% [1]. TMZ the cytotoxic effect derived from its DNA bases strong methylation, [5] on tumor cell a nucleic acid, protein and peptide nucleophilic occurred. Under alkaline conditions, TMZ rapid fracture methyl diazonium ion formation activity, compared to the surrounding tissue has a higher alkaline pH due to brain tumor, its easy tumor activated, gathering. CCNU, a nitrosourea alkylating agent, is easy through the blood-brain barrier is clinically more frequently used chemotherapy drug for treatment of intracranial malignant glioma, and much less toxic. In the treatment of intracranial tumors, the literature [2,5  7] generally believed that TMZ efficacy, show good prospects. ZENG Xian from [6] reported 38 cases of glioma postoperative chemotherapy TMZ, the effective rate of 44.74%, significantly higher than the the CCNU Group 11.77% (P <0.05), pointed out that TMZ more than CCNU reduce the tumor volume to improve the patient’s clinical symptoms, improve their quality of life. 2005, Stupp et al [7] for a comprehensive evaluation of radiotherapy plus adjuvant temozolomide with the same period of chemotherapy and radiotherapy alone for efficacy of newly diagnosed high-grade glioma patients in a clinical phase III study. The results showed that the two groups, the median survival time of 14.6 months and 12.1 months; 2-year survival rates were 26.5% and 10.4%, respectively: median tumor progression survival time was 6.9 months and 5.0 months, and adverse reactions are very slight. The results of this study show that the two sets of efficiency by rank sum test difference was statistically significant (U = 1.9675, P = 0.0245). The TMZ group average survival time (14.5 ± 2.5) months, significantly higher than CCNU group (10.5 ± 1.5) months (t = 7.7611, P = 0.000). The TMZ group nausea, vomiting, fatigue and the adverse reaction rate was 31.3%, significantly lower than CCNU group 56.3% (χ 2 = 4.0635, P = 0.0437). TMZ group was significantly lower than the degree of bone marrow suppression CCNU group (U = 3.2314, P = 0.0006). Further showed that TMZ death in the acceleration of glioma cells, reduce the tumor volume, to slow tumor recurrence and prolong the lives of patients and other aspects with better clinical efficacy, worthy of clinical application.