Management of Malignant Pericardial Effusion With Instillation of Mitomycin C in Non-Small Cell Lung Cancer
Management of Malignant Pericardial Effusion With Instillation of Mitomycin C in Non-Small Cell Lung Cancer
Management of Malignant Pericardial Effusion With Instillation of Mitomycin C in Non-Small Cell Lung Cancer
doi:10.1093/jjco/hyi019
Original Articles
Background: To evaluate the clinical efficacy and safety of mitomycin C in the local control of
malignant pericardial effusion, we carried out a trial of pericardial drainage with local instillation
of mitomycin C in eight patients who suffered from cardiac tamponade or symptomatic large
pericardial effusion caused by advanced non-small cell lung cancer.
Methods: After complete removal of the pericardial effusion by an ultrasound-guided inserted
catheter, 2 mg of mitomycin C was instilled into the pericardial space via the catheter.
Results: The drainage catheter was successfully removed in all patients. The duration of
pericardial drainage ranged from 7 to 14 days (median 10.5 days). Six of the eight patients
achieved a complete remission of pericardial effusions without any adverse effects.
Conclusion: Intrapericardial instillation of 2 mg of mitomycin C was feasible and demonstrated
a promising response against malignant pericardial effusion resulting from non-small cell lung
cancer.
Case Age/sex PS Prior Amount of Duration of Adverse Discharged Response Survival after
therapy effusion (ml) drainage (days) effects from hospital treatment (days)
1 51/M 3 CT + RT 1140 11 None Yes CR 92
2 45/M 2 CT 1594 10 None Yes CR 364
3 51/F 4 CT + RT 1560 7 None Yes CR 241
4 40/M 4 CT + RT 1870 7 None Yes CR 47
5 56/F 3 CT + RT 1102 13 None No Failure 30
6 69/M 4 CT 880 14 None No Failure 16
7 58/M 3 None 2827 12 None Yes CR 123
8 69/M 4 CT 1125 10 None Yes PR 68*
PS, performance status (Eastern Cooperative Oncology Group); CT, systemic chemotherapy; RT, thoracic radiation.
*Still alive.
Jpn J Clin Oncol 2005;35(2) 59
radiotherapy, systemic chemotherapy or percutaneous balloon in the intravesical instillation of mitomycin C for superficial
pericardiotomy have been employed for malignant pericardial bladder cancer and considering the side effects in the study of
effusion (1,10–12). However, most of the studies on these Lee et al. (8) and the performance status of patients. In this
measures were carried out with small patient numbers, so study, we assessed the feasibility of a mitomycin C intraperi-
no standard treatment for this condition has yet been estab- cardial administration through insertion of an ultrasound-
lished. The evaluation of clinical efficacy is also difficult guided catheter. The drainage catheter was successfully
because the treatment of malignant effusions varies depending removed in all patients; seven patients required only one
on the patients’ clinical conditions and underlying malignancy. instillation of mitomycin C. Also, the general condition of
In particular, the presence of pericardial effusion in patients those six patients who responded markedly improved and they
with non-small cell lung cancer indicates a grave prognosis, could be discharged from hospital. Afterwards, all responders
and surgical approaches to malignant effusion are applicable except for one (case 8) remained free of effusion recurrence.
only for limited cases. Therefore, treatment with an initial Among the five CR patients, two patients died due to pleuritis
pericardiocentesis followed by indwelling pericardial catheters carcinomatosa and pneumonia on days 47 and 92, but remained
is currently appropriate, since radiation therapy and systemic free of recurrence of effusion until death.
chemotherapy are not helpful in controlling the pericardial Tetracycline hydrochloride and cisplatin are toxic, with a
effusion secondary to lung cancer. It has still not been estab- high rate of adverse effects including arrhythmia, chest pain,
lished whether intrapericardial administration of a sclerosing nausea or fever, and bleomycin sulfate is also toxic, with a low
or cytotoxic agent is superior to pericardiocentesis followed by rate of adverse effects including arrhythmia or fever (1–6).
drainage due to the lack of a prospective comparative study. No adverse effects were observed including complication of
However, a review paper summarizing previous reports showed indwelling pericardial catheters under electrocardiographic
that pericardiocentesis has an overall success rate of 44.4%, guidance during this study.
indwelling pericardial catheters of 76.3%, and intrapericardial Among the other 13 patients who were not eligible for
administration of all sclerosing or cytotoxic agents of 81.6%, intrapericardial instillation of mitomycin C, seven patients
so intrapericardial instillation is a reasonably effective treat- responded (response rate 53.8%, 95% CI 25.1–80.8), five
ment for malignant pericardial effusion (10). patients could be discharged from hospital and four patients
Lee et al. (8) reported that the instillation of 8 mg of mito- had reaccumulation of fluid. The number is small and we
mycin C, dissolved in 10 ml of saline, in the pericardial space have not carried out a randomized study comparing the intra-
via the catheter every day or every other day has demonstrated pericardial administration of mitomycin C versus pericardial
excellent results, although they did not describe the response to drainage alone. Therefore, these results are not appropriate
treatment of lung cancer-related malignant pericardial effusion for comparison. However, the response rate, improvement
and improvement in the general condition of the 20 patients. in general condition and efficacy in preventing effusion
Malignant pericardial effusion was managed in 14 of 20 reaccumulation tended to be higher in the patients who were
patients (response rate 70%) without acute complications. administrated mitomycin C.
However, one patient developed pericardial constriction The present study demonstrated that the 2 mg mitomycin C
secondary to intrapericardial instillation of mitomycin C after instillation is feasible and has a promising response against
6 months and died suddenly due to ventricular arrhythmias malignant pericardial effusion with acceptable toxicity and it
8 months after the pericardial sclerosing therapy (13). Thus, could be a feasible treatment for patients of poor performance
the instillation of mitomycin C seems to have efficacy and status. A further trial is warranted to explore the efficacy and
short-term safety, but the concern regarding long-term safety safety of mytomycin C intrapericardial instillation in malignant
seems to remain. effusion due to advanced-stage non-small cell lung cancer.
Mitomycin C is a very potent vesicant drug. Therefore,
the dosage and administration of mitomycin C should be
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