Lung cancer is the major cause of MPE, and lung cancer patients with MPE tend to show particularly poor prognosis. MPE is a potentially fatal complication of cancer. However, the appropriate treatment for intrapericardial adhesion in cancer pericarditis has not yet been determined. In this study, we investigated the effectiveness and feasibility of intrapericardial administration of CBDCA (150 mg/body) in patients with lung cancer.
The response rate (CR and PR) to treatment was 66.7%, even though 5 of 21 patients, including those with small cell carcinoma, were NE and died within 30 days of treatment. The number of cases NE was higher when cases of SCLC with poor prognosis were included in the current analysis. On the other hand, a response rate of 72.3% was seen when the analysis was limited to patients with NSCLC; this is comparable to the findings of previous studies conducted in patients with NSCLC [8-11]. In the current analysis, seven patients treated with systemic chemotherapy, and MPE was regulated; the median survival period from intrapericardial instillation of CBDCA until death or censored was 71 days; this is similar to or slightly shorter than that reported in previous studies (Table 5) [8-11]. Of the 14 patients who underwent pericardial adhesion and responded well, 7 received subsequent systemic chemotherapy, and 12 were discharged from the hospital. This may benefit patients who are responsive to pericardial adhesion. The median duration of drainage was 9.5–10.5 days in patients with NSCLC, comparable to that described in previous reports [10,11]. Grade 1-2 adverse events were observed, but there were no grade 3 or higher serious adverse events or treatment-related deaths caused by intrapericardial administration of CBDCA. Based on these results, this treatment may be considered effective and feasible, keeping in mind that it was a retrospective study involving patients with a condition that shows poor prognosis. However, this study included cases from 2005, which was before the introduction of immune checkpoint inhibitors and kinase inhibitors for the treatment of driver gene mutation-/translocation-positive cases. The effectiveness and feasibility of intrapericardial CBDCA in combination with kinase inhibitors and immune checkpoint inhibitors remain unclear and should be further investigated.
Of the 21 patients included in the current study, 14 had CR or PR after pericardial adhesion, and 7 received systemic chemotherapy after pericardial adhesion. None of the patients who did not respond to pericardial adhesion or died within 30 days of pericardial adhesion received subsequent systemic chemotherapy. The median survival after pericardial adhesion in the 14 patients who responded to pericardial adhesion was 140.5 days (ranging from 31-2435 days), and the median survival after pericardial adhesion in the 7 patients who received systemic chemotherapy was 158 days (ranging from 69-2435 days). Of the seven patients who received subsequent treatment, two received kinase inhibitors and six were given cytotoxic drugs. Six of the cases were adenocarcinoma, while one was large cell carcinoma. Although it is difficult to draw definitive conclusions form the small number of cases analyzed, our data showed that patients responding to pericardial adhesion showed prolonged survival when they were subsequently administered systemic chemotherapy.
Moriya et al. demonstrated that intrapericardial instillation of CBDCA (300 mg) in patients with NSCLC was effective in controlling MPE in nine of ten patients [11]. Their method involved administrating 300 mg CBDCA and 100 mg lidocaine dissolved in 50 mL normal saline via the tube into the pericardial space. Following instillation of the drugs, the drainage tube was clamped and reopened after 40 minutes. In our analysis, 150 mg CBDCA dissolved in 20 mL normal saline was administered through a drainage tube, after clamping for 2 hours. This dose was chosen keeping in mind the small body size of Japanese patients. Furthermore, we chose a longer clamping duration, since a previous report showed that a concentrated dose of CBDCA in pericardial effusion was effective in killing tumor cells 1.5 hours beyond reopening the catheter, and a dilute dose of CBDCA in the plasma allowed the control of MPE with minimal systemic toxicity. This approach helped insure that the intrapericardial instillation of CBDCA was appropriate for patients who cannot tolerate systemic anticancer agents. We noted no apparent differences in the safety and efficacy between 150 mg and 300 mg CBDCA administered intrapericardially. Therefore, a dose of 150 mg CBDCA may be suitable in clinical practice.
There were several limitations to the current analysis. Firstly, this investigation was a retrospective study; therefore, we could not investigate late cardiac complications, which may introduce bias in the results of our study. Secondly, in contrast to most prospective studies, our exploratory study was not limited to patients who were in good condition or could be expected to show good prognosis for a certain period. Therefore, the results of this study are likely to more closely reflect the outcomes of clinical practice, since many patients do tend to be in poor condition, such as those with cancerous pericarditis. Thirdly, the current study did not compare intrapericardial instillation of CBDCA with pericardial drainage alone. The cases of carcinomatous pericarditis requiring treatment for pericardial effusion in lung cancer are rare. The low incidence makes it difficult to conduct a prospective trial assessing pericardial adhesion in an adequate number of patients with a single cancerous tumor.
In conclusion, the current study demonstrated that intrapericardial instillation of CBDCA (150 mg/body) is feasible, shows acceptable toxicity, and induces a promising response to lung cancer-associated MPE. However, given the small number of patients and the retrospective nature of the study, further studies are required to explore the effectiveness and feasibility of intrapericardial instillation of CBDCA in patients with lung cancer-associated MPE.