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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 5  |  Page : 84-88

Predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall lung cancer patients in China: A retrospective institution analysis of 132 patients


1 Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province; Zhejiang Key Laboratory of Diagnosis and Treatment Technology Research on Chest Tumor (Lung, Esophagus), Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, People's Republic of China
2 Department of Pharmacy, Integrated Chinese and Western Medicine Hospital, Hangzhou 310003, Zhejiang Province, People's Republic of China
3 Zhejiang Key Laboratory of Diagnosis and Treatment Technology Research on Chest Tumor (Lung, Esophagus), Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province; Department of GCP, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, People's Republic of China
4 Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, People's Republic of China

Date of Web Publication31-Aug-2015

Correspondence Address:
Dr. Lin Weng
Department of GCP, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province
People's Republic of China
Dr. Qing-Lin Li
Department of Pharmacy, Zhejiang Cancer Hospital, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310022
People's Republic of China
Dr. Zeng Wang
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province
People's Republic of China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.163849

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 > Abstract 

Objective: To investigate the predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall cell lung cancer (NSCLC) patients in China.
Methods: Medical records of 132 patients who underwent chemotherapy from January 2008 to December 2010 in our hospital were retrospectively reviewed. The response of first-line gemcitabine (GEM) and platinum doublets chemotherapy was evaluated, and the overall survival (OS) of all patients was followed. Further, risk factors of receipt cytotoxic second-line chemotherapy or not were identified and evaluated by univariate analyses.
Results: Sixty-six cases have undergone cytotoxic second-line chemotherapy for lung cancer. The OS between patients received first-line GEM plus platinum doublets chemotherapy and patients without cytotoxic second chemotherapy had no statistical difference (P = 0.73). Smoking or not might be a meaningful predictor for cytotoxic second-line therapy among these patients in this investigation (P < 0.05). Other factors, such as age (≥65 or < 65), gender, alcohol use, hypertension, diabetes mellitus, histology type, number of cycles of first-line chemotherapy, and response of first-line chemotherapy had no statistical difference between patients received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy (P > 0.05). In the sub-analysis, we found that the OS between patients received first-line GEM plus platinum doublets chemotherapy and patients without cytotoxic second chemotherapy had statistical difference in the population whose OS < 540 days (P = 0.019). Moreover, in these patients, the blood type was found to be a selected factor in receiving cytotoxic second-line chemotherapy or not (P < 0.05). Whereas other factors were not shown their selected effect (P > 0.05).
Conclusion: This study demonstrated that though the essentiality of cytotoxic second-line chemotherapy for stage IIIa-IV EGFR mutation indefinite NSCLC is unclear, patients who are blood type AB with poor prognosis and short OS might be a dominant population for cytotoxic second-line chemotherapy.

Keywords: Cytotoxic second-line chemotherapy, nonsmall cell lung cancer, overall survival, predictor


How to cite this article:
Cheng B, Cai XJ, Chen LY, Wang Z, Weng L, Li QL. Predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall lung cancer patients in China: A retrospective institution analysis of 132 patients. J Can Res Ther 2015;11, Suppl S1:84-8

How to cite this URL:
Cheng B, Cai XJ, Chen LY, Wang Z, Weng L, Li QL. Predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall lung cancer patients in China: A retrospective institution analysis of 132 patients. J Can Res Ther [serial online] 2015 [cited 2019 Sep 16];11:84-8. Available from: http://www.cancerjournal.net/text.asp?2015/11/5/84/163849


 > Introduction Top


For several decades, lung cancer has been the most commonly diagnosed malignancy and the leading cause of cancer-related mortality in both developed and developing countries. Nonsmall cell lung cancer (NSCLC) including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, is the most common form of lung cancer, accounting for approximately 80% of all lung cancers. [1],[2] Two-thirds of patients with lung cancer are diagnosed in locally advanced or metastatic disease. Platinum-based chemotherapy is considered as the main therapeutic approach for the above population. [3],[4] Traditionally, platinum doublet therapy reached a therapeutic plateau with an objective response rate of 30-40% and a median survival time (MST) of 8-10 months for patients with stage IIIb or IV disease, [5],[6] thus, a second-line therapy is required upon disease progression. The second-line therapy might provide the MST of 5-8 months in selected patients. [7],[8]

Though, there are reliable prognostic factors to identify lung cancer patients received first-line chemotherapy, the overall survival (OS) between patients only received first-line chemotherapy and patients received cytotoxic second-line chemotherapy, as well as predictors for lung cancer patients who could benefit from the cytotoxic second-line therapy, were not clear. Now-a-days, several clinical studies have identified that the Karnofsky Performance Status (KPS) and response and tolerance of first-line chemotherapy were associated with receipt of second-line chemotherapy. [3],[9] Moreover, David found socioeconomic status and symptom burden are also related to the receipt of second-line chemotherapy in patients with advanced NSCLC. [10]

As the available knowledge on the predictors for lung cancer patients who could benefit from the second-line therapy is limited, the present study was carried out to investigate the OS between patients received first-line gemcitabine (GEM) plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy as well as predictors for cytotoxic second-line therapy in hospitalized lung cancer patients (IIIa-IV) enrolled from January 2008 to December 2010 in a third-level university hospital.


 > Methods Top


General data

This study was approved by the Zhejiang Cancer Hospital Ethic Committee.

Data concerning lung cancer patients who had undergone chemotherapy in a medical team of our hospital from January 2008 to December 2010 were collected (to reduce the subjective differences in the treatment group). Cancer staging was determined as IIIa-IV by means of TNM classification with definite pathologic diagnosis, the hospital information system was used to review the information of the 132 lung cancer patients.

Inclusion criteria

(1) They had histologic or cytologic diagnosis of stage III or IV NSCLC; (2) 18 years or older in age; (3) receiving first-line GEM plus platinum doublets chemotherapy.

Data analysis on related factors

For each patient, the following demographic data were recorded: Age (≥65 or <65), gender, smoking status, alcohol use, hypertension, diabetes mellitus, and blood type. Disease variables recorded included date of diagnosis and date of death or last known follow-up. Histology was categorized as adenocarcinoma, squamous cell carcinoma, or other. Moreover, following treatment variables were recorded: Number of cycles of first-line chemotherapy, the response of first-line chemotherapy, and receipt of cytotoxic second-line chemotherapy.

OS was defined as the interval between the date of diagnosis and date of death or last follow-up.

Statistical analysis

The data were analyzed using version 15.0 of the SPSS (Version 15.0, purchase by SPSS company) software package. Overall data were screened using the Chi-square test to find risk factors with a statistical significance which was assigned with P < 0.05.


 > Results Top


Study population

From August 2008 to March 2010, 132 IIIa-IV lung cancer patients who received first-line GEM plus platinum doublets chemotherapy were analyzed including 100 male patients and 32 female patients. The median age of these patients was 56 (30-72) years, of which 66 cases underwent cytotoxic second-line chemotherapy for lung cancer. Among them, the number of patients with a KPS score ≥ 90 was 63 (47.7%), 69 patients (52.3%) were ever-smokers, 40 patients (32.5%) had drinking history, 20 patients (15.2%) had hypertension, and three patients (2.3%) had diabetes mellitus. The blood type data were as follows: Twelve cases were type AB (9.1%), 41 cases were type A (41.1%), 22 cases were type B (16.7%), 42 cases were type O (31.8%), and 13 cases (9.8%) had no records. Sixty-five cases were diagnosed with stage IV (46.8%). Pathological investigation revealed adenocarcinomas 52 (39.4%), squamous cell carcinomas 65 (49.2%), and other types 15 (11.4%). Moreover, 36 patients (27.3%) had family tumor history. The detailed information was summarized in [Table 1].
Table 1: Baseline characteristics of 132 advanced NSCLC patients


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Second-line therapy treatment and survival analysis

Among the 66 patients received cytotoxic second-line therapy, the median OS was 399 days. In detail, 57 patients received docetaxel for second-line therapy, eight patients received pemetrexed for second-line therapy, and one patient received other second-line therapy. Between the groups which received second-line chemotherapy and without second-line chemotherapy, the OS had no significant difference (P = 0.73, χ2 = 0.119) [Figure 1]. However, the sub-analysis showed that patients received second-line chemotherapy had longer OS in the population whose OS was <540 days (P = 0.019, χ2 = 5.466) [Figure 2].
Figure 1: Survival curve of 132 advanced nonsmall cell lung cancer patients. Blue-line: No second-line chemotherapy group, green-line: Second-line chemotherapy group

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Figure 2: Survival curve of advanced nonsmall cell lung cancer patients with overall survival <540 days. Blue-line: No second-line chemotherapy group, green-line: Second-line chemotherapy group

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Predictors analysis

According to [Table 2], smoking or not might be a meaningful predictor for cytotoxic second-line therapy among these patients in this investigation (P < 0.05). Other factors, such as age (≥65 or <65), gender, alcohol use, hypertension, diabetes mellitus, histology type, number of cycles of first-line chemotherapy, and response of first-line chemotherapy had no statistical difference between patients received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy (P > 0.05). Moreover, in the population whose OS < 540 days [Table 3], the blood type was found to be a selected factor in receiving cytotoxic second-line chemotherapy or not (P < 0.05). Whereas other factors were not shown their selected effect (P > 0.05).
Table 2: Univariate analysis of risk factors for receipt of second-line chemotherapy or not in lung cancer patients


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Table 3: Univariate analysis of risk factors for receipt of second-line chemotherapy or not in lung cancer patients whose OS<540 days


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 > Discussion Top


For advanced NSCLC, customized treatment based on the tumor histology and genetic profiles have become the standard of care. [11] It is known to all that NSCLC with EGFR mutation are dominant population for targeted therapy. [12],[13],[14] Nevertheless, EGFR detection has not yet been a routine assay for NSCLC in China, chemotherapy tends to be more popular, and the effect of cytotoxic second-line chemotherapy on this EGFR mutation indefinite population is unclear.

In addition, though platinum-based chemotherapy in advanced NSCLC is considered the first choice, these patients eventually experience disease progression and require second-line therapy. In recent years, few data on single institution experiences regarding predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV lung cancer patients in China have been published. Thus, the aim of this study was to investigate the related matters in the patients receiving cytotoxic second-line treatment or not.

The current study showed that the OS between patients only received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy had no statistical difference. However, at present there are instances that some patients who did not receive second-line chemotherapy had a better prognosis and longer OS than those who received. Thus, how to separate the population who really need second-line chemotherapy treatment? In our sub-analysis, we unexpectedly found that the OS between patients just received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second-line chemotherapy had statistical difference in the population whose OS < 540 days. It might be suggested that advanced NSCLC patients who had longer OS (more than 540 days) were not benefited from cytotoxic second-line chemotherapy. It remains ambiguous whether advanced NSCLC patients received second-line treatment would ensure prognostic knowledge for survival. Is there an excessive treatment situation exist? Moreover, the result of our study might approve the existing possibility of excessive treatment.

Prognostic factors are not enough to predict the efficacy of second-line chemotherapy, though it might be concluded that help in making a choice on a treatment should be based according to prognostic factors. [15],[16] In our investigation, for predictors of cytotoxic second-line therapy in these patients, smoking or not might be a meaningful factor. Other factors, such as age (≥65 or <65), gender, alcohol use, hypertension, diabetes mellitus, histology type, number of cycles of first-line chemotherapy, and response of first-line chemotherapy were not predictors for the receipt of cytotoxic second-line chemotherapy. Moreover, in the population whose OS < 540 days, the blood type was a selected factor between patients only received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy. It indicated patients who are blood type AB with poor prognosis be a dominant population for cytotoxic second-line chemotherapy and it was an interesting founding. There are few reports mentioned the selected effect of blood type on cytotoxic second-line chemotherapy choice making.

There are also some limitations in our investigation. As single-institution experiences are inadequate to make universal conclusions, this might be the major limitation. Furthermore, it was a retrospective study with a small sample size. Moreover, the EGFR mutation situation was indefinite. Moreover, even a strong statistical association does not necessarily indicate a cause-and-effect relation. Thus, to remedy these limitations, a prospective randomized controlled trial is needed.


 > Conclusion Top


In this EGFR mutation indefinite IIIa-IV NSCLC population, the importance of knowing the predictors of cytotoxic second-line chemotherapy is essential for the choice making. Moreover, the impact of cytotoxic second-line chemotherapy for these patients is unclear, which deserved further investigation in future in China.

Acknowledgments

This work was sponsored by Zhejiang Provincial Program for the Zhejiang Medical and Health Science and Technology Program (2014KYB036) and the special scientific research fund for Zhejiang Key Laboratory of Diagnosis and Treatment Technology Research on Chest Tumor (Lung, Esophagus), the general research program of medical health in Zhejiang Province (No. 2014KYB039), Science and Technology in Zhejiang Province Chinese Medicine Program (2012ZA101), Hangzhou city Science and Technology Project Planning Guide (Social Development) (20130733Q15) and Hangzhou City Health Science and Technology Project (2013A43).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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