What was the Effect of Taxol in Non-Metastatic Non-Small Cell Lung Cancer Patients in Mansoura University Hospital?

Introduction: Lung cancer has been turned from a rare disease to a worldwide problem. Non-small cell lung cancer (NSCLC) is the most commonly diagnosed type of lung cancer forming about 85% of all cases. Measures for treatment in NSCLC include: surgical resection, radiotherapy, chemotherapy and targeted therapy. They can be used as solo modality or in combination. Taxanes as paclitaxel and docetaxel are important classes of chemotherapeutic agents. Aim of the work: The aim of our retrospective study is to evaluate the role of taxol based chemotherapy in treatment of non-metastatic NSCLC. Patient & methods: Between January 2008 and December 2013, thirty five patients with newly diagnosed, nonmetastatic NSCLC were included for this analysis. Between January 2008 and December 2013, thirty five patients with newly diagnosed, nonmetastatic NSCLC were included for this analysis. The patients received paclitaxel containing regimens. All were combined either with carboplatin (33 patients) or with cisplatin (2 patients). Results: As regard response rate only one patient achieved complete response, partial response was detected in 18 patients, stationary disease was demonstrated in 12 patients and 4 patients had progressive disease. The most common toxicity was the hematological toxicity. The median PFS was 8 months (95% Confidence Interval, 6.774 -9.226 months). The median OS was 13 months (95% Confidence Interval, 10.533 –15.467 months). Conclusion: Taxol is active class of chemotherapeutic agents in NSCLC and well tolerated.


Introduction
Lung cancer has been turned from a rare disease to a worldwide problem. The deaths in USA were 160,340 in 2012 due to lung cancer. In USA, it was responsible for 28% of all cancer mortality. Changing the location does not affect markedly the global lung cancer mortality, with 43% of deaths occurring in more developed countries and 57% occurring in the developing regions Ridge et al. [1]. Non-small cell lung cancer (NSCLC) is the most commonly diagnosed type of lung cancer forming about 85% of all cases. It grows up and spreads much slowly than small cell lung cancer Barzi  . The aim of our retrospective study is to evaluate the role of taxol based chemotherapy in treatment of non-metastatic NSCLC in the term of response rate (RR) and toxic profile then to assess progression free survival (PFS) and overall survival (OS). e. Adequate bone marrow, liver, and kidney functions (haemoglobin ≥ 9g/dl, platelet ≥100,000/l, WBCs ≥3000/l provided that absolute neutrophil count (ANC) ≥1500/l and serum creatinine ≤1.5 upper limit of normal).

f.
No prior treatment with chemotherapy.
This study was approved by the Ethical Committee of Faculty of Medicine, Mansoura University. The collected data from patient's sheets included the history from all patients as age, sex and smoking habit. General examination was done including weight, height and surface area. Performance status was assessed according to Eastern Cooperative Oncology Group (ECOG). Tumor staging for all patients were documented according to TNM staging system. Investigations included pathological, radiological and laboratory investigations.

Treatment Regimens
Thirty five patients were included in this study. The patients received paclitaxel containing regimens. All were combined either with carboplatin (33 patients) or with cisplatin (2 patients). In most of patients the schedule of paclitaxel used was ranged from 175 -200 mg/m 2 IV infusion over 3 h every 3weeks ,only 4 patients received paclitaxel 75 mg/m 2 IV infusion weekly. The number of cycles ranged from 4 to 8 and the median number was 6. All patients were received pre-medications as recommended. Symptoms and signs of toxicities were assessed either hematological toxicities or non-hematological toxicities. Toxicities were reported according to the Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. The primary end point in our research was to assess the RR and the toxic profile and the secondary end points were to assess PFS and OS.

Statistical Analysis
The data was collected, coded, processed and analyzed using SPSS (statistical package for social sciences) version 16. Qualitative data were described using number and percent.
Associations between categorical variables were tested using Chi-square test (c2). Monte Carlo test was used whenever there was one or more cell counted 5 or less. Continuous variables were presented as mean ± SD (standard deviation) and Median (min -max). The two groups were compared with Student t test (parametric data) P-value considered significant if ≤ 0.05. The survival functions were tested using Kaplan-Meier.  Between January 2008 and December 2013, thirty five patients with newly diagnosed, non-metastatic NSCLC were included for this analysis. Patient's characteristics and tumors features were mentioned in Table 1. As regard response rate only one patient (3%) achieved complete response (CR), partial response (PR) was detected in 18 patients (51.5%), stationary disease (SD) was demonstrated in 12 patients (34 %) and 4 patients (11.5%) had progressive disease as summarized in Table 2. The most common toxicity was the hematological toxicity. Leucopenia was detected in 5 patients (14%); (grade I was 5.7 %), (grade II was 5.7 %), and (grade III was 2.8 %). Thrombocytopenia was found only in one patient (2.8%) and was grade I. Three patients (8.5%) developed anemia during therapy, 2 patients (5.7 %) was grade I anemia and 1 patient (2.8%) was grade II. Other adverse effects as peripheral neuropathy was observed in 3 patients (8.5%), grade I was in one patient and grade II was detected in 2 patients (5.7 %). Two patients (5.7 %) suffered from grade II emesis. Also diarrhea was noticed in 2 patients (5.7 %). Less common toxicities were observed as rising serum creatinine as shown in Table 3. Survival analysis was done for this study showed that median PFS was 8 months (95% Confidence Interval, 6.774 -9.226 months) as shown in Figure  1. The median OS was 13 months (95% Confidence Interval, 10.533 -15.467 months) as shown in Figure 2.

Cancer Therapy & Oncology International Journal Discussion
Our study was a retrospective study included 35 patients with non-metastatic NSCLC received taxol based chemotherapy. It showed male predominance 57% and female percentage was 43% in comparable to the study of Liao WY et al.
[8] at 2013 with male 52% and female percentage48% Liao et al. [8]. In our study 94 % of patients had stage III disease. Complete response (CR) was achieved in one patient(3%) and 20 patient (51.5 %) showed partial response (PR) with overall response rate (ORR) (54.5%) , while Kocher F and his colleagues at 2014 evaluated response after induction of docetaxeland cisplatin in 78 chemonaïve patients with NSCLC stage II, IIIA and IIIB. Partial response to induction therapy was observed in 43 patients (55%) Kocher et al. [9]. Liao WY and his colleagues at 2013demonstrated the efficacy of taxanes among 62 patients with stage III N2 NCSLC, CR was detected in one patient (2%) and PR was achieved in 25 patients (40%) with ORR (42%) Liao et al. [8]. Other studies as Chen YM et al.
The median OS in our study was 13 months (95% Confidence Interval, 10.533 -15.467 months) which cope with Bonomi P et al. [13] results. Their study included 599 patients to Compare OS and life quality in advanced non-small-cell lung cancer patients treated paclitaxel combined with cisplatin versus etoposide with cisplatin. The median survival duration for the stage IIIB subgroup in paclitaxel arm was13.1 months. A randomized phase II study compare weekly paclitaxel versus vinorelbine in combination with cisplatin against inoperable chemo-naïvenonsmall-cell lung cancer included 140 patients.
The median survival time was 11.7 months in the paclitaxelcisplatin arm Y Chen et al. [14]. Also the results obtained in our series are better than Fossella F et al. [15], Sandler A et al. [16], Lynch TJ et al. [17] and Zhu J et al. [18] with OS 11.3, 10.3, 8.38 , 8.9 months respectively. This difference could be attributed to larger sample size in these studies; also these studies included stage III and IV disease, so their OS lower than the OS in our study. Regarding PFS in our study was 8 months and were higher than Chen YM et al.
The commonest toxicity in our study was the hematological toxicity. Other adverse effects as peripheral neuropathy was observed in 3 patients (7.5%), 2 patients (5%) suffered from grade II emesis and diarrhea was noticed in 2 patients (5%) only. On the other hand; Kosmidis P et al. [22] demonstrated mild toxicities in paclitaxel and carboplatin combinations for the treatment of advanced non-small-cell lung cancer. Grades ¾ neutropenia, thrombocytopenia, and anemia were seen in (15%) and (15%), (2%) respectively Kosmidis et al. [22]. Inoue A et al. [12] assessed toxicities of weekly paclitaxel combined with carboplatin in elderly patients with advanced NSCLC.
The most Common toxicities were hematological; Grades ¾ leucopenia, thrombocytopenia, and anemia were observed in (30%), (15%), (13%) respectively, while peripheral neuropathy and nausea were detected only in 3% of patients. The higher hematological toxicities in this study could be explained by the old age that may be liable for more adverse events Inoue et al. [12]. Scagliotti GV and his colleagues reported at 2010 the adverse effects of carboplatin and paclitaxel in chemotherapynaïve patients with advanced NSCLC. Neutropenia was 7%, thrombocytopenia was 3%, Anemia was 9%, peripheral neuropathy was 13%, vomiting was 7%, diarrhea was 13 % and oral mucositis was 2% Scagliotti et al. [23].

Conclusion
In conclusion in our study; taxol are active class of chemotherapeutic agents in NSCLC and well tolerated. This agent exhibit clinical differences that can affect the choice of agents. However, further studies with longer follow up are needed for better orientation and comparisons with other agents.

Disclosure
The authors have no conflicts of interest to disclose.