Research of neo-Adjuvant TC chemotherapy regimen result and expression rates of some markers related to tongue cancer at stages III and IV (M0)”

litaxel 175mg/m2 in day 1; Cisplatin 100 mg/m2 in day 2. Response and side effect statuses were evaluated after each cycle. After 3 cycles, a medical consultancy was did to decide whether patients should continue to receive surgery or radiotherapy or a combination of 2 methods. Patients continued to be monitored for overall survival after treatment. All information was fully recorded according to consistent medical record form. 2.2.4. Data analysis: Information was encoded and processed by SPSS 20.0 software. - Average rate, standard deviation, maximum and minimum values were calculated. - A comparison of statistical significance test with p < 0.05. OS was analyzed by the Kaplan - Meier method. The Log-rank test method was used to compare overall survival between two groups. Chapter 3: RESULTS After doing a study on 125 patients from 2012 to 2018, we had some following conclusions: 3.1. SOME CLINICAL AND HISTOPHATHOLOGICAL CHARACTERISTICS OF STUDIED PATIENT GROUP 3.1.1. Age and gender Table 3.1. Distribution of age and gender Age Male Female Summary Pts % Pts % Pts % ≤ 40 5 4 3 2,4 8 6,4 41 - 50 36 28,8 11 8,8 47 37,6 51 - 60 39 31,2 9 7,2 48 38,4 ≥ 61 18 14,4 4 3,2 22 17,6 Sum 98 78,4 27 21,6 125 100 Observation: Average age was 52.5 ± 8.6, age group from 41 to 60 is the most common, accounting for 76%. Male / female ratio was 98/27 = 3.6/1. 3.1.2 Disease’s stage Table 3.7. Distribution of T-N stage clinically   N  T N0 N1 N2 N3 Sum Pts % Pts % Pts % Pts % Pts % T2 0 0 1 0,8 10 8 1 0.8 12 9,6 T3 26 20,8 13 10,4 2 1,6 0 0 41 32,8 T4 33 26,4 36 28,8 3 2,4 0 0 72 57,6 Sum 59 47,2 50 40,0 15 12,0 1 0,8 125 100 Observation: Among 125 patients, there were 72 stage-4 patients, which reached the highest rate (57.6%). Patients at stages N0 and N1 were 47.2% and 40% respectively, accounting for the highest rates. 3.1.3. Treatment methods Table 3.10. Treatment methods Methods Pts % Resect half tongue + resect lymph nodes or half tongue + resect lymph nodes + resect jaw bone 63 50,4 Post-neoadjuvant chemo radiotherapy 62 49,6 Sum 125 100 Observation: 63 patients received surgical inventions to resect half tongue + resect lymph nodes or half tongue + resect lymph nodes + resect jaw accounted to 50.4% (therein, 2 patients were resected half tongue + resected lymph nodes + resected jaw). 62/125 patients received post-chemo radiotherapy, accounting for 49.6%. 3.2. RESPONSE AND SIDE EFFECTS STATUSES 3.2.1. Response status according to chemotherapy course Table 3.11. Response status after chemotherapy cycles Respone status CR PR SD PD ∑ Pts % Pts % Pts % Pts % Cylce I 0 0 31 24,8 93 74,4 1 0,8 125 Cycle II 0 0 66 52,8 58 46,4 1 0,8 125 Cycle III 18 14,4 55 44 46 36,8 6 4,8 125 After 3 cycles 18 14,4 55 44 46 36,8 6 4,8 125 Observation: After 3 cycles, complete response rate was 14.4%, parital response rate accounted for 36.8%, non-remission rate was 36.8%; progressive disease accounted for 4.8%. Response rate increased gradually through chemotherapy cycles. 3.2.2. Response status after 3 cycles Table 3.12. Response status by age and gender after 3 cycles Response status  Factors CR+PR SD +PD p Pts % Pts % Age (n=125) ≤ 50 34 61,8 21 38,2 P = 0,492; OR = 1,28 CI 95% 0,62-2,64   > 50 39 55,7 31 44,3 Gender (n=125) Male 54 55,1 44 45,9  P=0,154;  OR = 0,51 CI 95% 0,21-1,29   Female 19 70,4 8 39,6 Observation: Response status by age and gender didn’t have a statistically difference. Table 3.13. Response status by T, N Stage CR+PR SD +PD Tổng p Pts % Pts % Pts * T(n=125)  T2 3 25 9 75 12 0,041 T3 24 58,5 17 41,5 41 T4 46 63,9 26 36,1 72 * N (n=125)    N0 43 72,9 16 27,1 59 P=0,002  N1,2,3 30 45,5 36 55,5 66 * Stage (n=125)   III 24 64,9 13 36,1 37 P=0,342  IV 49 55,7 39 44,3 88 Observation: Response rates of patients with stage T4 and T3 disease were 63.9% and 58.5% respectively, while 72.9% and 45.5% were response rates of nodal metastasis and non-nodal metastasis groups respectively. Stage-III patient’s response rate was higher than that of stage-IV patient. Table 3.14. Response status by histological grade Histological grade CR+PR SD +PD ∑ p Pts % Pts % Pts I 10 52,6 9 47,4 19 P=0,853  II 46 59,7 31 40,3 77 III 17 58,6 12 41,4 29 Observation: Response rates of patients with histological grades 1, 2 and 3 were 52.6%, 58.6% and 59.7% respectively. 3.2.3. Patient rates were designated to receive surgery or radiotherapy after 3 chemotherapy cycles Table 3.15. Designation of surgery or radiotherapy after neo-adjuvant chemotherapy. Methods Surgery Radiation Pts % Pts % T   T2 5 4 7 5,6 T3 26 20,8 15 12 T4 35 28 37 29,6 Sum 66 52,8 59 47,2 N N0 34 27,2 25 20 N1,2,3 32 25,6 34 27,2 Sum 66 52,8 59 47,2 Observation: After 3 cycles, patient rate designated to receive radiotherapy was 47.2%. 3.2.4. Cell degeneration after chemotherapy Table 3.16. Cell degeneration rate Cell degeneration rate Pts % <5% 6 9,5 5 - 49% 28 44,4 50 - 99% 20 31,8 100% 9 14,3 Tổng 63 100 Observation: Among 66 patients designated to receive surgery, there were 63 people receiving surgery. Post-operative histopathological result showed that 14.3% of patients had no cancer cell. Table 3.17. Cell degeneration rate by stage Rate ≤ 50 % > 50 % ∑ p Pts % Pts % Pts % T T2 7 11,1 2 3,2 9 14,3  P=0,118 T3 10 15,9 15 23,8 25 39,7 T4 17 27,0 12 19,0 29 46,0 N N0 16 25,4 19 30,1 35 55,5 P=0,142 N1,2,3 18 28,6 10 15,9 28 44,5 Observation: When all participants were divided into 2 groups: cell degeneration rate ≤ 50% and cell degeneration rate > 50% groups for comparation of degeneration level after treatment with factors such as T, N and disease’s stage. We didn’t found any statistically difference. 3.2.5. Side effects Table 3.19. Side effects on hematology, liver and kidneys after 3 chemotherapy cycles. Times / ∑ Cycles % Low hemoglobin 186/375 49,6 Leukopenia 256/375 68,3 Low granulocytes 102/375 74,7 Thrombocytopenia 53/375 14,1 Elevated SGOT 50/375 13,3 Elevated Creatinine 17/375 4,5 Observation: low hemoglobin rate acconted for 49.6%; leukopenia rate was 68.3%, low granulocytes rate was 74.7%; thrombocytopenia rate was 14.1%. Elevated SGOT and creatinin rates were 13.3% and 4.5% respectively. 3.2.5.2. Side effects on hematology by treatment cycle Table 3.20. Side effects on hematology Level 0 Level I Level II Level III Level IV ∑ Pts % Pts % Pts % Pts % Pts % Hemoglobin Cycle I 74 59,2 43 34,4 5 4,0 3 2,4 0 0 125 Cycle II 61 48,8 42 33,6 19 15,2 3 2,4 0 0 125 Cycle III 54 43,2 44 35,2 24 19,2 3 2,4 0 0 125 Leukopenia Cycle I 57 45,6 14 11,2 18 14,4 37 29,6 12 9,6 125 Cycle II 50 40,0 17 13,6 19 15,2 26 20,8 13 10,4 125 Cycle III 57 45,6 13 10,4 17 13,6 28 22,4 10 8 125 Granulocytes Cycle I 30 24,0 15 12,0 17 13,6 35 28,0 28 22,4 125 Cycle II 33 26,4 16 12,8 12 9,6 31 24,8 33 26,4 125 Cycle III 32 25,6 13 10,4 19 15,2 29 23,2 32 25,6 125 Thrombocytopenia Cycle I 108 86,4 16 12,8 1 0,8 0 0 0 0 125 Cycle II 106 84,8 19 15,2 0 0 0 0 0 0 125 Cycle III 108 86,4 17 13,6 0 0 0 0 0 0 125 Observation: Low hemoglobin maily occurred at grades 1 and 2. Grade-4 leukopenia accounted for 6.7%. There was no patient with thrombocytopenia at grades 3 and 4. 3.2.5.3. Side effects on liver and kidneys by treatment cycle Table 3.21. Side effects on liver and kidneys by treatment cycle Level 0 Level I Level II Level III Level IV ∑ Pts % Pts % Pts % Pts % Pts % SGOT  Cycle I 98 78,4 26 20,8 1 0,8 0 0 0 0 125 Cycle II 109 87,2 16 12,8 0 0 0 0 0 0 125 Cycle III 118 94,4 7 5,6 0 0 0 0 0 0 125 Creatinin  Cycle I 122 97,6 3 2,4 0 0 0 0 0 0 125 Cycle II 120 96,0 5 4,0 0 0 0 0 0 0 125 Cycle III 116 92,8 9 7,2 0 0 0 0 0 0 125 Observation: Grade-II elevated SGOT level only occurred in the first course, accounting for 0.8%. There was no patient with elevated creatinin level at grade 2, 3 or 4. 3.2.5.5. Other side effects Table 3.22. Distribution of other side effects by patient Side effects Level 0 Level I Level II Level III Level IV Sum Pts % Pts % Pts Pts % Pts % Pts Nausea 34 27,2 39 31,2 25 20 27 21,6 0 0 125 Vomitting 61 48,8 24 19,2 18 14,4 22 17,6 0 0 125 Mucositis 110 88,0 8 6,4 2 1,6 0 0 0 0 125 Nerve pain 78 62,4 41 32,8 6 4,8 0 0 0 0 125 Fatigue 20 16,0 89 71,2 16 12,8 0 0 0 0 125 Observation: Other side effects maily occurred at grades I, II; and didn’t occur at grade IV. 3.3. OVERALL SURVIVAL Overall survival Chart 3.1. Graph of overall survival Table 3.23. Table of 1-year, 2-year, 3-year, 4-year and 5-year overall survivals OS 1 year 2 year 3 year 4 year 5 year % 78,4 60,2 46,5 37,2 24,1 Observation: 5-year overall survival rate was 24.1%. Average overall survival was 36.48 ± 2.23 months. 3.4. RATES OF EXPRESSION OF P53, EGFR AND HER2 MARKERS AND SOME FACTORS RELATED TO OVERALL SURVIVAL 3.4.1. Rates of expression of p53, EGFR and Her2 markers Rate of expression of EGFR marker Chart 3.1. Rate of expression of EGFR marker Observation: Rate of EGFR-positive expression was 36.8% Correlation between EGFR expression status with pathological characteristics Table 3.24. Correlation between EGFR status with pathological characteristics Factors Positive (Pts) Negative (Pts) Sum (Pts) p Age ≤ 50 21 34 55 P = 0,776; OR = 1,11 CI 95% 0,53-2,31  > 50 25 45 70 Gender Male 38 60 98 P = 0,383; OR = 1,50 CI 95% 0,60-3,77 Female 8 19 27 T T2,3 14 39 53 P = 0,039; OR = 0,44 CI 95% 0,21-0,97   T4 32 40 72 N Positive 23 36 59 P = 0,632; OR = 1,19 CI 95% 0,58-2,47   Negative 23 43 66 Stage III 9 28 37 P = 0,049 IV (M0) 37 51 88 Histological grade I 9 10 19 P = 0,216 II 30 47 77 III 7 22 29 Response status CR + PR 25 48 73 P = 0,483 SD + PD 21 31 52 Observation: There was a correlation between EGFR expression status with stage T and disease’s stage. There was no correlation between expression of EGFR status with age, gender, nodal metastasis, histological grade, response status. Rate of expression of Her2 marker Chart 3.3. Rate of expression of Her2 marker Observation: Rate of expression of Her2-positive was 4.8% Correlation between expression of Her2 status with pathological characteristics Table 3.25. Correlation between expression of Her2 status with pathological characteristics Factors Positive (Pts) Negative (Pts) Sum (Pts) p Age ≤ 50 4 51 55 P = 0,252; OR = 2,67 CI 95% 0,47-15,13  > 50 2 68 70 Gender Male 6 92 98 P = 0,188; OR = 0,94 CI 95% 0,89-0,99   Females 0 27 27 T T2,3 2 51 53 P = 0,645; OR = 0,67 CI 95% 0,12-3,78   T4 4 68 72 N Positive 6 60 66 P = 0,018; OR = 1,1 CI 95% 1,02-1,19   Negative 0 59 59 Stage III 0 37 37 P = 0,104 IV (M0) 6 82 88 Histological grade I 0 19 19 P = 0,459 II 5 72 77 III 1 28 29 Response status CR + PR 4 69 73 P = 0,674 SD + PD 2 50 52 Observation: There was a correlation between expression of EGFR status with nodal metastasis status (N). There was no correlation between expression of EGFR status with age, gender, stage T, disease’s stage, histological grade, response status. Rate of expression of p53 marker Chart 3.4. Rate of expression of p53 marker Observation: Rate of expression of p53-positive was 33.6% Correlation between expression of p53 status with pathological characteristics Table 3.26. Correlation between expression of p53 status with pathological characteristics Factors Positive (Pts) Negative (Pts) Sum (Pts) p Age ≤ 50 24 31 55 P = 0,035; OR = 2,24 CI 95% 1,05-4,76  > 50 18 52 70 Gender Male 30 68 98 P = 0,178; OR = 0,55 CI 95% 0,23-1,32   Female 12 15 27 T T2,3 18 35 53 P = 0,941; OR = 1,03 CI 95% 0,49-2,18   T4 24 48 72 N Positive 19 40 59 P = 0,755; OR = 0,89 CI 95% 0,42-1,87   Negative 23 43 66 Stage III 10 27 37 P = 0,313 IV (M0) 32 56 88 Histological grade I 8 11 19 P = 0,218 II 28 49 77 III 6 23 29 Response status CR + PR 27 46 73 P = 0,342 SD + PD 15 37 52 Observation: There was no correlation between expression of p53 status with gender, stage T, nodal metastasis status, disease’s stage, histological grade, response status. 3.4.2. Some factors related to overall survival 3.4.2.1. 5-year overall survival by T Chart 3.5. Graph of 5-year overall survival by T Observation: overall survival rates of grades T2 and T3 groups, which were 39.4% and 6.5% respectively, were higher than that of grade T4 group. Difference was statistically significant with p=0.025. 3.4.2.2. 5-year overall survival by N Chart 3.6. Graph of 5-year overall survival by N Observation: overall survival rate of N0 group was higher than that of nodal metastasis group, overall survival rates of two groups were 35.1% and 10.0% respectively with p = 0.000. 3.4.2.3. 5-year overall survival by stage Chart 3.7. Graph of 5-year overall survival by stage Observation: Stage-III patient’s 5-year overall survival was 48.1%, which was much higher than that in stage-IV patient as 7.9%. Difference was statistically significant with p= 0.002. 3.4.2.4. 5-year overall survival by treatment method Observation: overall survival rate of post-neoadjuvant-chemotherapy surgery group was 44.4%, which was much higher than that in post-neoadjuvant-chemotherapy combined chemotherapy and radiotherapy group as 29.0% with p= 0.005. 3.4.2.6. 5-year overall survival by response to neoadjuvant-chemotherapy Chart 3.10. Graph of 5-year overall survival by response to neoadjuvant-chemotherapy Observation: overall survival rate of response group was 36.7%, which was higher than that in non-response group (11.6%). Difference was statistically significant with p=0.002. 3.4.2.7. Correlation between EGFR expression status with overall survival Chart 3.11. 5-year overall survival by EGFR expression status Observation: overall survival of EGFR-postive group was shorter than that in EGFR- negative group. Difference was statistically significant with p= 0.016. 3.4.2.8. Correlation between Her2 expression status with overall survival Chart 3.12. 5-year overall survival by Her2 expression status Observation: Correlation between Her2 expression status and overall survival wasn’t seen 3.4.2.9. Correlation between p53 expression status with overall survival Chart 3.13. 5-year overall survival by p53 expression status Observation: Correlation between p53 expression status and overall survival wasn’t seen CHAPTER 4. DISCUSSION 4.1. SOME CLINICAL AND PATHOLOGICAL CHARACTERISTICS 4.1.1. Age and gender In our study, 95.6% of patients were above 40 years old, while the most common age-group was from 41 to 60 years old (accounting for 76%). This result was also similar to those of domestic and foreign authors. A study of Fabio et al showed that the most common age-group was from 41 to 60 years old, accounting for 46%. Nguyen Van Tai’s study in 2018 showed that age-group above 50 accounted for the majority, while age-group from 51 to 60 years old was the most common. All TC studies showed that male patient rate was higher that of female, a possible reason was that men receive many negative effects from many risks causing tongue cancer such as smoking, drinking alcohol... Male / female ratio in our study was 3.6/1, which was suitable with Pham Cam Phuong’s study, reported that male / female ratio was 4.5/1. Stefan’s study (2013) on 6241 tongue-cancer patients showed that male / female ratio was 2.88/1. 4.1.2. Disease’s stage Our result showed that among 125 patients, there was 12 patients with stage T2 disease (9.6%), all of them had cervical nodes and positive cytology results; 41 patients with stage T3 disease (32.8%), 72 stage T4 patients (57.6%) with invasive lesions of anterior tonsil pillar, mouth floor, and/or tongue muscles. Stage N: Our result was similar to those of other authors. A study of Zhong et al. (2012) on 256 tongue-cancer in situ patients showed that patient rates with stages N0, N1 and N2 disease were 43%, 36.7% and 20.3% respectively. Recruited patients had stages III and IV (M0) disease, after stage arrangement, rates of patients with stages III and IV disease were 32% and 68% respectively. With people group similar with that of above, Le Van Quang’s study also showed a similar result with 27.4% of patients at stage III, and 72.6% of patients at stage IV. A comparison of correlation between stage T and clinical nodal metastasis showed a difference: stage T4 had a higher nodal metastasis rate (31.2%). 4.2. RESPONSE AND SIDE EFFECTS STATUSES 4.2.1. Response to neo-adjuvant chemotherapy Chemotherapy regimen Pre-operative chemotherapy was usually applied for advanced cancers of head, face and neck. Initial studies used CF regimen. Then, some authors added taxane (docetaxel and palitaxel) to CF regimen to make TCT regimen. This new regimen showed a higher response rate, but also more side effects. In Vietnam, most patients had average BMIs, poor intakes and were difficult to tolerate a 3-drug regimen. So, cisplatin combined with taxane (docetaxel and palitaxel) could help patients achieve high response rates and good tolerances. General response rate by chemotherapy cycles In our study, all patients received full treatments for 3 cycles. Response status was increased gradually by chemotherapy cycles. After 3 cycles, complete response rate was 14.4%, parital response rate accounted for 36.8%, non-remission rate was 36.8%; progressive disease accounted for 4.8%. Till now, no author in Vietnam has reported neo-adjuvant chemotherapy result by this regimen, however, some studies for other regimens for patient-group like ours were did. According to Le Van Quang’s result of CF regimen study, complete response rate was 12%, parital response rate accounted for 50.4%, non-remission rate was 30.8%; progressive disease accounted for 6.8%. Salama et al. did a Phase-II study on 222 patients with recurrent and metastatic head and neck cancer at stages III and IV (M0) treated by TC regimen followed by simultaneous chemotherapy and radiotherapy for radical treatment, his result showed that complete response rate was 75%. Similarly, Vokes (2003) showed a complete response rate after using neo-adjuvant TC chemotherapy for 69 patients with recurrent and metastatic head and neck cancer in situ as 75.3%. CF and TC are the most common 2-drug regimens. Both of them had high complete response rates, helping reduce sizes of tumor and lymph nodes, facilitate future surgery for radical treatment. Response rate by disease’s stage In our study, response rates after using 3 chemotherapy cycles for patients with stages III and IV disease were 64.8% and 55.7% respectively. There was a difference of response levels between stages T and N with p < 0.05. After doing a study on neo-adjuvant Paclitxel and Cisplatin regimen on patients with head and neck squamous cell carcinoma at stage IV, Stefano (2011) reported a response rate after 3 chemotherapy cycles of 74.4% for this stage. The author thought that his response rate was higher than that in some other studies due to more chemotherapy cycles used and higher dose for Paclitaxel on his study. Designation of surgery after 3 chemotherapy cycles by disease’s stage After 3 neo-adjuvant TC cycles, 66 patients were designated to receive surgery, accounting for 52.8%. So, pre-operative neo-adjuvant chemotherapy significantly contributed to reduce sizes of tongue tumor and cervical nodes to make surgery more easy. In 2003, Licitra reported his study on 195 with oral squamous cell carcinoma, study’ result showed that neo-adjuvant chemotherapy helped reduce mandibulotomy rate [83]. Post-treatment cell degeneration According to Zhong, patient-group with a good response on histopathology, that is only below 10% of cancer cells remained on their specimens, had overall and progression-free survivals higher significantly than those in poor-response group. Among 63 operated patients, 9 people had no cancer cell on their post-operative specimens, accounting for 14.3%. However, this result didn’t absolutely reflect histopathological response rate of the regimen because we didn’t do any re-biopsies for patient-group treated by post-chemotherapy radiation. Our study result was different from results of other authors, this was due to our study only implemented on tongue squamous cell carcinoma, but not on other sites in the oral cavity. 4.2.2. Side effects 4.2.2.1. Side effects on hematology, liver and kidneys Chemotherapy drugs didn’t only affect to cancer cells, but also normal cells of the body, especially cells having fast division speeds such as cells lining the digestive tract, hair cells, red blood cells, and white blood cells. This factor affected to patient’s treatment course and life quality, patients may be even died due to chemotherapy drugs. Side effects on hematology Low hemoglobin Among 375 patients treated by chemotherapy, 129 people got grade-1 low hemoglobin (34.4%), 48 patients had grade-2 low hemoglobin (12.8%). When doing a comparision with other studies, which also used TC regimen or other 2-drug regimens or even 3-drug TCF regimens, results were similar. Rajesh et al (2018) also studied 70 patients with stage T4 oral cancer, 56 people were treated by TC regimen, his result showed that only 2 patients had low hemoglobin at grade 3 or 4 (3.6%). Stefano et al (2011) studied 43 patients with recurrent and metastatic head and neck cancer at stage IV (M0) from January, 1999 to December, 2002 by neo-adjuvant TC chemotherapy regime. After 3 cycles, 10 patients had low hemoglobin at grades 1 and 2 (23.3%), and no patient had low hemoglobin at grade 3 or 4. Therefore, TC regime helped reduce side effect of low hemoglobin. Leukopenia Before treament, all patients had normal leukocyte and granulocyte counts, but during taxane and cisplatin combination regimen, grade-3 leukopenia occured on 91/375 cycles, accounting for 24.3%. Grade-4 leukopenia rate was 9.3%. Grade-3 leukopenia rates on courses I, II and III were 29.6%; 20.8% and 22.4 respectively. Grade-4 leukopenia rates on courses I, II and III were 9.6%; 10.4% and 8.0% respectively. Leukopenia rates at grades 3 and 4 were 25.3% and 24.8% respectively (caculated by 375 cycles). Gibson (2005) stated that TC regimen had a lower side effect of leukopenia compared to that of CF regimem. So, leukopenia rate at our patient-group treated by TC regimen was similar to results of other author around the world, and was lower than CF patient-group. Thrombocytopenia In our study, thrombocytopenia rate after 3 cycles was 14.1% (rates of patient with stages 1 and 2 thrombocytopenia were 13.9% and 0.2% respectively, no thrombocytopenia patient was at stage 3 or 4). Thrombocytopenia rate by each cycle: cycle 1 (12.8%), cycle 2 (15.2%), cycle 3 (13.6%). Another study by Basaran (2013), a study on using TC regimen on 50 patients with recurrent and metastatic recurrent and metastatic head and neck cancer, showed that thrombocytopenia condition was uncommon, it mainly occured at grades 1 and 2 (3.9% and 1% respectively), both thrombocytopenia rates at grades 3 and 4 were 1%. Gibson reported that rates of thrombocytopenia patient at grades 3 and 4 treated by TC regimen were 3% and 1% respectively. When comparing with CF, TC regimen had fewer thrombocytopenia. Thus, TC regimen also showed little side effect on thrombocytopenia, if any, it mainly occured at mild level, grades 1 and 2. Toxicities on liver and kidneys TC regimen rarely caused elevated liver enzymes. In our study, grade-II elevated SGOT was only seen in coruse I with a rate of 0.8%. Most pts had grade-I elevated SGOT. Cisplatin caused a severe accumulation of side effects on the kidneys. However, our result showed that there was no patient with elevated creatinine level at grades 2, 3 and 4. Grade 1 elevate creatinine level were 2.4%, 4.0% and 7.2% at courses 1, 2 and 3 respectively. Foreign authors also reported similar results. According to Stefano et al. (2011), TC regimen rarely caused side effects on liver and kidneys, there were no patient with elevated creatinine or liver enzyme level at grades 3 and 4. In general, side effects on hematology, liver and kidney