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Publication date 2017 Journal SM Lung Cancer: Research & Therapy Volume 1 Issue 1 Pages 1002 Publisher SMGroup Background: Malignant pleural effusion is a common problem in patients with advanced malignancies and compromised the short-lived survival of these patients. These effusions can be resistant to the treatment such as systemic chemotherapy, pleurodesis with sclerosantagents and recurrent drainage. Therefore, new therapeutic options are needed. The purpose of this study was to evaluate the effectiveness of intrapleural chemotherapy with Cisplatin for the management of MPE in lung, breast and mesothelioma cancers. Materials and methods: Twenty-one cancer patients with MPE were enrolled in this study. Cisplatin was injected through a catheter at a dose of 30mg /m2, and this procedure was performed 3 times at intervals of two weeks. Patients were evaluated for side effects and responses to the treatment every two weeks and one month after the last treatment. Results: Among the assessable 18 patients, complete response and partial response were 9 (50%) and 4 (22.2%) patients, respectively (overall response rate 72.2%). Dyspnea was improved in 13 (72.2%) patients and had no change in 5 (27.8%) patients. One patient did not refer after the first intrapleural injection. Also two patients died during the study. None of the patients had side effects of grade 3 and 4. Conclusion: The results of this trial study showed that using of Intrapleural Chemotherapy with cisplatin in the management of patients with MPE in lung, breast and mesothelioma cancers is effective and safe.
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How to cite this article Kiani A, Taghavi K, Esmaeilzadeh M, Khosravi A, Seifi S,
Abedini A. Evaluation of Intrapleural Chemotherapy with Cisplatin in Iranian Cancer
Patients with Malignant Pleural Effusion. SM Lung Cancer Res Ther. 2017; 1(1): 1002.
OPEN ACCESS
Introduction
Malignant Pleural Eusion (MPE) occurs in most patients with advanced cancer [1] and
accounts for 15 to 35 percent of all pleural eusions [2]. Most MPEs are caused by metastases,
especially in lung cancer, in more than one-third of cases and in breast cancer in the latter stages [3].
Variety of symptoms such as progressive dyspnea, cough and chest pain reduces the quality of the
short-lived survival of these patients [4] and in some cases can be fatal and therefore, it is associated
with poor prognosis and signicant mortality and morbidity [1]. Despite all treatments such as
surgery, chemotherapy and radiotherapy, survival rates in primary pulmonary cancer patient with
MPE are low [5]. is eusion usually does not respond to systemic chemotherapy and treatment
is mostly symptomatic [6]. In many patients, tubal drainage and pleurodesis are used to control
plural eusion by injecting sclerosing agents, but the failure to respond to pleurodesis require
frequent necessity for drainage through a chest tube, leading to multiple visits to medical centers
and extended hospitalization and greater risk of infection [4-7], thus new approaches in therapy are
essential. One of these treatments is Intra Pleural Chemotherapy (IPC) with anticancer drugs that
have been studied in interventional therapy. Mentioned treatment is performed locally, so systemic
side eects are minimized and the procedure is quite eective [8]. In patients who did not respond to
Systemic Chemotherapy or for any reason were not candidates for Chemotherapy, IPC can reduce
the accumulation of pleural uid and relieve the patient’s symptoms and improve their quality
of life [9]. One of the new therapeutic interventions of IPC is anticancer drugs, which has been
studied in interventional procedures. A study in South Korea showed that IPC with Cisplatin and
Cytarabine was eective in the treatment of MPE in Cervical Carcinoma with multiple pulmonary
and cerebral metastases [1]. Also, other studies in Japan and China have proven the ecacy of IPC
in the treatment of MPE [10].
Accordingly, the present study was designed to evaluate the eect of IPC with cisplatin in the
treatment of MPE in an Iranian population.
Research Article
Evaluation of Intrapleural
Chemotherapy with Cisplatin in Iranian
Cancer Patients with Malignant Pleural
Eusion
Arda Kiani1, Kimia Taghavi2, Maryam Esmaeilzadeh2, Adnan Khosravi3, Sharareh
Sei4, Atefeh Abedini2*
1Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Disease (NITLD), Shahid Beheshti University of Medical Sciences, Tehran,
Iran
2Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Disease (NITLD), Shahid Beheshti University of Medical
Sciences, Tehran, Iran
3Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Disease (NITLD), Shahid Beheshti University of Medical
Sciences, Tehran, Iran
4Medical Hematology/ Oncology, National Research Institute of Tuberculosis and Lung Disease (NITLD), Shahid Beheshti University of Medical Sciences, Tehran,
Iran
Article Information
Received date: Aug 30, 2017
Accepted date: Sep 13, 2017
Published date: Sep 18, 2017
*Corresponding author
Atefeh Abedini, Chronic Respiratory
Diseases Research Center, National
Research Institute of Tuberculosis
and Lung Diseases (NRITLD), Shahid
Beheshti University of Medical
Sciences, Tehran, Iran
Email: dr.abedini110@sbmu.ac.ir
Distributed under Creative Commons
CC-BY 4.0
Keywords Malignant pleural effusion;
Intrapleural chemotherapy; Cisplatin
Abstract
Background: Malignant pleural effusion is a common problem in patients with advanced malignancies and
compromised the short-lived survival of these patients. These effusions can be resistant to the treatment such as
systemic chemotherapy, pleurodesis with sclerosantagents and recurrent drainage. Therefore, new therapeutic
options are needed. The purpose of this study was to evaluate the effectiveness of intrapleural chemotherapy
with Cisplatin for the management of MPE in lung, breast and mesothelioma cancers.
Materials and methods: Twenty-one cancer patients with MPE were enrolled in this study. Cisplatin was
injected through a catheter at a dose of 30mg /m2, and this procedure was performed 3 times at intervals of two
weeks. Patients were evaluated for side effects and responses to the treatment every two weeks and one month
after the last treatment.
Results: Among the assessable 18 patients, complete response and partial response were 9 (50%) and
4 (22.2%) patients, respectively (overall response rate 72.2%). Dyspnea was improved in 13 (72.2%) patients
and had no change in 5 (27.8%) patients. One patient did not refer after the rst intrapleural injection. Also two
patients died during the study. None of the patients had side effects of grade 3 and 4.
Conclusion: The results of this trial study showed that using of Intrapleural Chemotherapy with cisplatin in
the management of patients with MPE in lung, breast and mesothelioma cancers is effective and safe.
Citation: Kiani A, Taghavi K, Esmaeilzadeh M, Khosravi A, Seifi S, Abedini A.
Evaluation of Intrapleural Chemotherapy with Cisplatin in Iranian Cancer Patients with
Malignant Pleural Effusion. SM Lung Cancer Res Ther. 2017; 1(1): 1002. Page 2/4
Gr up
SM
Copyright Abedini A
Methods
Patients selection
is study was approved by Iranian registry clinical trials
(IRCT2017053134256N1). Cancer patients with pleural eusion who
referred to Massih Daneshvari Hospital from March 2016 to February
2017 were enrolled in this study. Among them, twenty-one cancer
patients with pleural eusion in lung, breast and mesothelium who
have positive cytology for malignancy, and have not responded to
systemic chemotherapy or have not responded to standard systemic
chemotherapy for any reason, were selected. Of all patients, the chest
X-ray was performed in order to estimate the initial degree of pleural
eusion. All patients gave written informed consent.
Treatment protocol
Aer insertion of the pleural catheter and dilution of the pleural
uid, cisplatin was injected through a catheter at a dose of 30 mg/m2,
and this procedure was performed 3 times at intervals of two weeks.
If pleural eusion was completely resolved aer the rst or second
injection, the injection was not repeated longer and only follow-up
was considered. Before each injection, Complete Blood Count (CBC),
kidney function test and electrolytes were examined for each patient
in order to investigate the side eects. e estimation of the amount
of pleural eusion in the chest X-ray and the comparison of each step
was made by the radiologist by naked eye. e complete response
to treatment was considered when pleural eusion completely
disappeared and did not recur aer four weeks. e relative response
was dened as a decrease in uid but with no complete disappearance
and improvement in the patient’s dyspnea and no accumulation
of the uid within four weeks aer the end of the treatment. No
response was dened as when the uid level did not change, or
increased within four weeks aer the end of the treatment. Out of
the 21 patients enrolled in the study, one patient did not refer aer
the rst intrapleural injection, due to dyspnea’s dislocation, and none
of analyzes was performed. Also two patients died during the study.
Statistical analysis
e data were collected and categorized into SPSS version 22.
Descriptive data are expressed as the mean ± standard deviations.
Nonparametric Wilcoxon and Kruskal-Wallis statistical tests were
used to determine the eect of IPC on the amount of pleural eusion
and dyspnea. P-value <0.05 was considered as signicant in all groups.
Result
Patients characteristics
In the period of March 2016 to February 2017, twenty one
patients from Massih Daneshvari Hospital were enrolled in this study
as shown in (Table 1). Out of 21 patients, 61.9% were men and 38.1%
women with mean age of 60.95 years and age range of 47 to 80 years.
Ten patients had MPEs as a consequence of primary metastatic lung
cancer (stage IV), 6 patients had MPEs due to breast cancer and 2
patients had MPEs owing to mesothelioma. Nineteen patients had a
history of systemic chemotherapy but 2 patients did not receive any
systemic chemo drug.
Drug administration
Out of 18 patients who completed the study, 50% (9 patients)
had a complete response to Cisplatin intra-pleural, 22.2% (4 patients)
had partial response and 50% had no response (Figure 1). Kruskal
Wallis test showed no signicant dierence in the amount of pleural
eusion, before the rst injection and in three periods of completed
response, partial response, and lack of response (P> 0.05).
e comparison between the two groups of pre-intervention and
post-intervention is presented in (Table 2) , during three dierent
period and based on the percentage of pleural eusion in chest X-ray,
using nonparametric Wilcoxon test statistics .e results of the test
showed a signicant dierence between all the groups (P=0.002).
Out of ten male patients who completed the study, 30% (3
patients) had completed response to intra-pleural cisplatin, 20% (2
patients) had partial response and 50% (5 patients) had no response.
Out of eight female patients who completed the study, 75% (6
patients) had completed response to intra-pleural cisplatin and 25%
(2 patients) had no response.
At the end of study, in response to intra-pleural cisplatin, out of
10 patients with lung cancer 4 cases had complete response, 2 cases
had a partial response and 4 cases had lack of response. Out of 6 cases
of breast cancer, 4 patients had complete response and 2 patients had
partial response. From 2 cases of mesothelioma, 1 case had complete
response and 1 case had no response (Figure 2).
Among 9 cases that responded to treatment, the completed
response was achieved in 2 cases in the rst follow-up, aer the rst
Table 1: Patient characteristics.
Patients(n=21) N Value
Gender
Male 13 (61.9%)
Female 8 (38.1%)
Age
Mean Age 60.95 years
Age Range 47-80 years
Histology
Lung Cancer (Stage IV) 13
Mesothelioma 2
Breast Cancer 6
N= Number of patients.
Figure 1: Frequency of distribution of patients based on response to Intra-
pleural Cisplatin.
Citation: Kiani A, Taghavi K, Esmaeilzadeh M, Khosravi A, Seifi S, Abedini A.
Evaluation of Intrapleural Chemotherapy with Cisplatin in Iranian Cancer Patients with
Malignant Pleural Effusion. SM Lung Cancer Res Ther. 2017; 1(1): 1002. Page 3/4
Gr up
SM
Copyright Abedini A
injection, in 4 cases in the second follow-up followed by the second
injection and in 3 cases in the third follow-up followed by the third
injection.
Table 3 shows the comparison of the two groups of pre-
intervention and post-intervention at three dierent times, based
on Borg dyspnea Scale, using the nonparametric Wilcoxon test. e
results of the test showed a signicant dierence in all groups (P<
0.05).
Side effects created during treatment
Following treatment anemia has been observed in 2 patients,
rombocytopenia grade II in 2 patients, Hypomagnesaemia grade I
in 4 patients and Hypokalemia grade I in one patient. Hypocalcemia
grade I and II was observed in three and one patient, respectively.4.
Discussion
e purpose of this study was to determine the eect of intra-
pleural cisplatin chemotherapy on the treatment of MPE. MPE is oen
the result of impaired pleural uid reabsorption due to mediastinal
lymph node obstruction that is responsible for drainage of pleural
uid [11]. Tumors that metastasize to these lymph nodes such as
lung, breast and lymphoma cancers are the most common causes of
MPE [12]. One of the main therapeutic priorities is the active control
of pleural eusion in order to improve the patient’s quality of life
[10]. One of these treatments is IPC with anticancer drugs. Cisplatin
is a known chemotherapeutic drug with anti-tumor activity [7] that
interacts with DNA and cause apoptosis and inhibition of cell growth
[13]. In the present study, twenty one cancer patients enrolled for
Cisplatin IPC. Out of 18 patients persisting by the end of the study,
9 patients (50%) had completed response, 4 (22.2%) had a partial
response and 5 patients (27.8%) had no response to treatment. Based
on these results, the total overall response rate of complete response
and partial response were 13 cases (72.2 %). Due to cisplatin, none
of the patients had hematologic and non-hematologic complications.
Nan Du et al. studied the eect of intra-pleural treatment
in combination with bevacizumab and cisplatin compared with
individual treatment only by cisplatin, in 72 patients with NSCLC.
At the end of the study, the overall response rate in the group just
receiving cisplatin (control group) was 50 percent. e response to
the treatment was evaluated weekly and through Pleural Sonography
(10), while in the present study, the response to treatment was
evaluated with chest X-ray. In a study by Figlin R et al. , performed
on 46 patients with MPE with cytological conrmation in a variety
of solid tumors, intra-pleural cisplatin injection was performed as a
single dose of 100 mg/m2 with 1200 mg of cytarabine via chest tube
and overall response rate (complete and partial) aer three weeks was
49 percent [13]. is is due to the injection that was performed only
in one cycle and the overall response rate was lower than the present
study, the more general response in this study can be attributed to
more frequent intra-pleural injection. In another study by Tetsuro
Baba and colleagues, in 8 out of 17 patients with NSCLC, IPC was
performed with cisplatin or Adriamycin but not with other IPC.
In the group under IPC, the survival rate was 88% but in non-IPC
group it was 44% (P = 0.04) and they concluded that IPC is eective
in these patients and improves postoperative survival [14]. In terms
of improved dyspnea, out of 18 patients examined, 13 cases (72.2%)
had improvement in dyspnea and in 5 cases (27.8%) no changes has
been observed. In the present study, twenty patients were examined
for the presence of any side eects aer treatment, no one shows
sign of leucopenia or neutropenia, renal dysfunction and hearing
impairment but only 2 patients show sign of anemia 2 patients
had thrombocytopenia, 1 patient had Hypokalemia, 4 patients had
Hypocalcemia, and 4 patients had Hypomagnesaemia. In terms of side
eects, in a study by Figlin R et al., a patient was diagnosed with grade
III nephrotoxicity, 4 patients had grade III hematologic complications
and 5 patients had grade III cardiovascular complications [13]. In a
study by Kee Won Kim et al., in 40 patients with NSCLC one cycle of
IPC with cisplatin at a dose of 100 mg/m2 and cytarabine at a dose of
1200 mg/m2 was performed via chest tube, and one case of death due
Table 2: The comparison of the two groups of pre-intervention and post-
intervention at three different times.
Mean ± SD P value
The amount of PE before the rst
injection 67.14 ± 21.36
The amount of PE before the
second injection 42.25 ± 25.62
The amount of PE before the third
injection 33.61 ± 32.44
The amount of PE one month after
the end of treatment 28.61 ± 36.69
*The mean of PE before the rst injection is compared with PE before the second
injection, third injection and PE one month after the end of the treatment.
*PE: Pleural effusion.
Figure 2: Frequency of distribution of response to Intra-pleural Cisplatin
based on the type of primary cancer.
Table 3: The comparison of the two groups (before and after the intervention
at three different times) in terms of Dyspnea according to the Borg Scale
questionnaire.
P Value
Comparison of
dyspnea rate before
the second injection
with dyspnea before
the rst injection
Comparison of
dyspnea rate before
the third injection
with dyspnea before
the rst injection
Comparison of
Dyspnea rate one
month after the end
of treatment with
dyspnea before the
rst injection
-3.686b-3.035b-3.160b
0.000 0.002*0.002*
b Based on positive ranks
* The mean of Dyspnea before the rst injection compared with the second
injection, third injection and one month after the end of treatment was statistically
signicant (mean reduction), P<0.05.
Citation: Kiani A, Taghavi K, Esmaeilzadeh M, Khosravi A, Seifi S, Abedini A.
Evaluation of Intrapleural Chemotherapy with Cisplatin in Iranian Cancer Patients with
Malignant Pleural Effusion. SM Lung Cancer Res Ther. 2017; 1(1): 1002. Page 4/4
Gr up
SM
Copyright Abedini A
to drug toxicity and one case of grade IV hematologic complications
have been observed [15]. Two patients had Empyema and wound
infections, but no signicant renal or hepatic toxicity was observed
in any of these patients [15]. e more severe side eects in these two
studies can be attributed to the simultaneous combination of cisplatin
and cytarabine, and also to the use of a higher dose of cisplatin (100
mg/m2).
In previous studies consistent with our study, no severe
therapeutic side eects such as grade III or IV has been observed. We
speculate that since the injection of cisplatin was performed locally
and within the pleural, no serious systemic side eects would be
expected.
Although due to the low sample size and the lack of uniformity
of the patients, it is not possible to compare and accurately evaluate
the types of cancers for the response to cisplatin in the intrapleural
injection.
According to the ndings of this study, it is suggested that breast
cancer has a better response to therapy than lung and mesothelioma
cancer. In conclusion, a larger sample size and matched patients are
required in order to compare the response of intrapleural cisplatin
injection in patients with lung cancer and breast cancer and
mesothelioma cancer.
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