Assessment Of Chemotherapy In Advanced Lung Cancer: Study Of Animal Experiment And Clinical Follow-up

Lung cancer continues to be the leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80% of cases. Systemic chemotherapy is the main treatment for the majority of patients with NSCLC because most are diagnosed with advanced inoperable disease. However, the role of chemotherapy is controversial for patients with advanced NSCLC. There are conflicting data on the contribution to survival of chemotherapy ,and the side reaction maybe aggravate patient's condition, many physicians consider that advanced stage patients don't tolerate chemotherapy well and maybe have a poorer prognosis than patients not chemotherapy. So it's important to study and research the significance of chemotherapy for advanced lung cancer.OBJECTIVE AND SIGNIFICANCE: The objective of this study is to investigate whether chemotherapy can increase the survival time and improve quality of life of patience with advanced-lung cancer. Provide experiment evidence for clinician in applying therapeutic regimen and evaluating curative effect. And investigate the characteristics of lung cancer cases to offer fundamental data of lung cancer for preventing and controlling the disease.METERLAILS AND METHODS:Ⅰ,Assessment of the use of paclitaxel and cisplatin in advanced Lewis lung carcinoma in C57BL/6 miceExperimental groups: The animals were randomly divided into 3 groups, a chemotherapy arm (n=20), a control arm (n=20) and a blank arm (n=12).Methods: An advanced lung cancer model was established in C57BL/6 mice. One group was treated with the standard therapeutic regimen of paclitaxel and cisplatin. The control group was injected only with 0.9% NaCl and a blank group received no injection .Survival time, mental state and weight of each group were recorded .Statistical analysis: the statistical significance of differences in survival and mental state among the groups were determined by One-way ANOVA and Kruskal-Wallis H. the method of repeated—measures ANOVA and One-way ANOVA were used to determine differences in weight loss among the groups. Multiple comparisons were determined by Dunnett T3. All statistical analyses were performed with SPSS 13.0 software. The value of P≤0.05 was defined as significant.Ⅱ,A Study on the Characteristics of Lung Cancer CasesCollected 1012 cases of lung cancer from Nan fang hospital diagnosed from 2000 to 2005. The cases include 730 males and 282 females. The first symptom and the symptom and physical sign before final diagnosis were recorded. Histories of smoking, age, gender, performance status, organ involvement, histological type were recorded too. And compare those between the males and females.Statistical analysis: statistical analyses were performed with SPSS 13.0 software. The statistical significance differences between the groups were determined by x~2 test. The value of P≤0.05 was defined as significant.Ⅲ,clinical follow-up study of patients with advanced-lung cancer on assessment of chemotherapyThis is a retrospective study of patients with advanced lung cancer admitted for treatment in Nanfang hospital. Clinical data were reviewed in the records of these patients from 2000 to 2005. All the patients meet the criteria and divided into 142 cases of chemotherapy group, 99 cases of supportive care group, according to the therapeutic methods. There were significance differences in age and KPS score between the two groups, so applied paired way to keep balance between the two groups. 25 cases were been deleted. 133 cases belong to chemotherapy group, and average age was 54.17±11.753 (20～82) . Supportive care group included 79 cases, and 59.96±12.289 (29～87) .Statistical analysis: statistical analyses were performed with SPSS 13.0 software. The x~2 tests were used to determine differences in gender, age, smoking, performance status, clinical stage, histological type and organ involvement between the groups. The statistical significance differences in curative effect and toxicity between both sexes in chemotherapy group were determined by x~2 test and Mann-Whitney Test. The method of Kaplan—Meier was used to determine actuarial survival. Differences in survival were determined by Log rank analysis. Cox regression proportional hazard model was used in analysis of the risk factors influencing the prognosis. Overall survival time was defined as the interval between initial diagnoses and the date of last consultation or until death. The value of P≤0.05 was defined as significant.RESULTS:Ⅰ,Assessment of the use of paclitaxel and cisplatin in advanced Lewis lung carcinoma in C57BL/6 mice1,The survival time of the experimental group was significantly greater than the control group and the blank group (P= 0.000) .2,On the second day after treatment there was no significant difference among the groups in their mental state (P=0.636) . On days three to seven after treatment, the experimental group had significantly better mental score index than the control group and the blank group (P<0.05 ) .3,On the second and third days after treatment, the experimental group had significant greater percent weight loss than the control group (P=0.030) and the blank group (P=0.003 ) . On days four to seven after treatment, the three groups were not significantly different in weight loss (P>0.05 ) .Ⅱ,A Study on the Characteristics of Lung Cancer Cases1,The rate of no symptom before final diagnosis was 7.91% in patients withlung cancer. Cough was the most common first symptom, account for58.89%; next was expectoration, 24.51%. The rate of anorexia, chest pain,chest distress, breathlessness as first symptom were 15.61 %, 17.39%, 9.19%, 9.98%, respectively. The rate of hoarseness, fever, dyspnea, emaciated asfirst symptom were 1.38%,3.56%,0.89%,1.98%. The rate ofsubcutaneous nodule or tumor, limbs numbness or asthenia, lumbodynia asfirst symptom were 4.46%, 3.46%, 4.47%, respectively. The rate ofdizziness and vomitus, acataposis, allolalia, pelvic limb pain, face and neckpuffiness were 0.99%,0%,0.2%,0.79%,0.79%, respectively.2,The ratio of male and female was 5 to 2 in patients with lung cancer, andaverage age was 58.5 (20～93) . The number of patients was low before 31years old, about 0.89%. The number reach peak in the fifth to seventh decades of life, and then begins to descent. The performance status was determined according to clinical data available in the records. The rate of patients with PS score of 80 was at most, about 45.62%. Adenocarcinoma was the predominant histological type, about 40.22 %( male 37.12, female 52.48). The second was squamous carcinoma, about 28.75% (male 32.88%, female 18.09). The ratio of small cell lung cancer was 7.91% (male 9.32%, female 4.26%). In addition, the rate of no histological type was 15.12%(male 13.7%,female 19.15%). Classification of clinical staging was obtained from the records, based on clinical motes or reports of imaging exams. The ratio of patients in earlier stage was about 14.13% (male 15.62%, female 11.35%). The ratio of patients in advanced stage was at most, about 71.71% (male 71.10%, female 80.49%). When diagnosis, the most common site of metastasis was bone (25.30%), then was brain (9.19%).3,There were not significantly different between male and female in constituent ratio of age (P=0.057) , PS score (P= 0.346) and organs involved (P=0.078) . But histological type (P=0.000) and TNM stage (P=0.017) had significant difference between both sexes.Ⅲ,clinical follow-up study of patients with advanced-lung cancer on assessment of chemotherapy1,There were no significant difference in constituent ratio of sex, age, smoking, KPS score, clinical stage, histological type and organ involvement between chemotherapy group and supportive care group (P>0.05) .2,For all patients in chemotherapy were given 497 cycles of therapy and the median number of cycles was 5.52, ranging from 1 to 14. cisplatin or carboplatin were the most common drugs employed, other frepuent drugs are paclitaxel, Gemcitabine, Navelbine, etoposide. In chemotherapy group, the overall response rate was 36.1% and the rate of no change, progressive disease were 45.1%, 18.8%, respectively. There was no significant difference in curative effect between both sexes (P=0.657) .3,The main blood toxicity was leucopenia, about 53.4%. Grade 3 or 4 leucopenia occurred in 26 patients (19.5%). The rates of grade 3/4 thrombocytopenia and anemia were 9.8%, 1.5%. Grade 3 or 4 nausea and vomiting occurred in 9 patients (6.8%). Toxicity could be tolerant. And there was no significant difference in toxicity between both sexes (P>0.05) .4,In chemotherapy group, the median survival was 16 months (95%CI: 13.576-18.424); response rate was 36.1%; one-year, two-year and three-year survival were 65.41%, 17.29%, 5.26%, respectively. In supportive care group, the median survival was 8 months (95%CI: 6.922-9.078) and one-year, two-year, three-year survival were 27.85%, 7.59%, 5.06%, respectively. The overall survival was significantly better for patients treated with chemotherapy compared to patients that only received supportive care (P=0.000). There were significantly different in one-year survival between two groups (P=0.000). But the two-year and three-year survival were no significant difference between two groups (P=0.075, P=0.949).5,There were no significant difference in median survival, one-year survival, two-year survival and three-year survival between male and female in chemotherapy group and supportive care group (P>0.05) .6,Cox regression prognostic analysis showed that KPS scores and therapy method were independent predictors of overall survival (P=0.000). The prognosis was well in the patients with advanced lung cancer at good performance and chemotherapy. CONCLUSIONS:1,The combination of paclitaxel and ciplatin can prolong the survival time andimprove quality of life of mice with advanced lung cancer.2,At present, adenocarcinoma was the most common histological type. Approximately 80% patients were in advanced stage, and have no chance to operate, but most of them have good performance status with PS score greater than 80. so they have chance to prolong survival time and improve quality of life through chemotherapy.3,The overall survival was significantly better for patients treated with chemotherapy compared to patients that only received supportive care, but chemotherapy could not improve long term survival compared to supportive care. There were no significant difference in tolerance and response to chemotherapy drugs between male and female.4,KPS scores and therapy method were independent predictors of overall survival. The prognosis was well in the patients with advanced lung cancer at good performance and chemotherapy. So patients with advanced lung cancer at good performance should treat with chemotherapy.