Purpose
Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or ...erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.
Methods
We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.
Results
EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months,
p
= 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone.
Conclusions
EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Malignant pericardial effusion (MPE) causes cardiac tamponade and an extremely poor outcome unless it is well controlled. The effect of pericardial drainage and the intra-pericardial instillation of ...bleomycin on the control of MPE was examined in this prospective multi-institutional phase II trial.
In eligible patients with cytologically defined MPE resulting from non-small cell lung cancer, the pericardial effusion of such cases was continuously drained. After complete drainage, 10 mg of bleomycin was then locally instilled via a catheter. The catheter was then removed if the total amount of drainage was less than 30 ml/day. If the catheter could not be removed within 5 days after treatment, bleomycin was administered one more time.
Among the 22 patients who entered this trial, the tube drainage catheter was successfully removed from 17 patients with one instillation, whereas four required such instillation twice and one required such instillation three times. No severe adverse events were observed, except for constrictive pericarditis, which resulted in the treatment-related death of one patient. The control rate of pericardial effusion was 95% ± 0.09 (95% confidence interval). No restoration of pericardial effusion was observed during the follow-up period or until death from any cause. Median survival time from the beginning of the protocol was 17.9 weeks.
Pericardial drainage followed by the instillation of bleomycin was found to be a safe and effective method for the management of MPE associated with non-small cell lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous ...reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE).
A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities.
Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%).
Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is rapidly expanding in Japan, an educational program for its safe performance should be immediately established.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is important to identify optimal regimens of cisplatin-based, third-generation chemotherapy and thoracic radiotherapy for patients with unresectable, Stage III, non-small cell lung cancer.
...Patients with unresectable, Stage III non-small cell lung cancer were treated with the following regimen: cisplatin 80 mg/m(2) on days 1 and 29, with irinotecan 60 mg/m(2) on days 1, 8, 15, 29, 36, and 43 and 30 mg/m(2) on days 57, 64, 71, 78, 85 and 92. Thoracic radiotherapy was started on day 57 at 2 Gy/day (total 60 Gy).
From February 1998 to January 1999, 68 patients were enrolled. Grade 3/4 toxicities during induction chemotherapy primarily included neutropenia (73.5%) and diarrhea (20.6%), while Grade 3/4 toxicities during concomitant thoracic radiotherapy with irinotecan consisted of neutropenia (18.4%), esophagitis (4.1%) and hypoxia (6.5%). There was one treatment-related death due to radiation pneumonitis. The response rate was 64.7% (95% confidence interval, 52.2-75.9%). The median survival time was 16.5 (95% confidence interval, 12.6-19.8) months. The 1- and 2 year survival rates were 65.8% (95% confidence interval, 54.4-77.1%) and 32.9% (95% confidence interval, 21.6-44.1%), respectively. Overall, only 36 (56%) completed both the scheduled chemotherapy and thoracic radiotherapy.
Induction chemotherapy with cisplatin plus irinotecan followed by low-dose irinotecan and concomitant thoracic radiotherapy was feasible according to the prespecified decision criteria in this study for patients with unresectable Stage III non-small cell lung cancer. We did not decide to select this regimen for further investigations because approximately half of the patients completed the scheduled treatment.
We retrospectively evaluated whether preoperative percutaneous transthoracic needle biopsy (PTNB) affected the incidence of pleural recurrence in pathological stage I lung cancer patients. Pleural ...recurrence occurred in pure solid nodule (PSN) cases but not in ground-glass nodule cases, as evaluated using thin-section computed tomographic imaging. When the cases were restricted to sub-pleural PSN, the incidence of recurrence tended to be higher in a PTNB group (63 patients diagnosed by PTNB) than in a non-PTNB group (86 patients diagnosed by transbronchial biopsy or intraoperative diagnosis) (25% vs. 4%, p =.050). PTNB should not be performed in patients with a sub-pleural PSN.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
It is not clear whether sequential chemotherapy can be performed immediately in patients with p-stage I non-small cell lung cancer recurring during a 2-year period of daily oral administration with ...tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had the increased risk of grade 4 neutropenia, but the overall survival was not inferior to that in patients who received chemotherapy beginning more than 1 month (n = 11). We could perform sequential chemotherapy immediately while paying attention to grade 4 neutropenia.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
It is not clear whether there is a difference in benefit of chemotherapy between small cell lung cancer (SCLC) patients with pre-existing idiopathic interstitial pneumonias (IIPs) and non-small cell ...lung cancer (NSCLC) patients with IIPs.
We performed a retrospective study of the overall survival (OS) between advanced lung cancer patients with IIPs (n=28) and those without IIPs (n=145).
The OS in NSCLC patients with IIPs was shorter than in those without IIPs (median OS, 10.6 vs. 27.9 months, p=0.008) but the OS in SCLC patients with IIPs was not inferior to that of those without IIPs (12.7 vs. 14.8 months, p=0.835). Multivariate analysis showed that the small number of regimens increased the risk of mortality, instead of pre-existing IIPs.
The continuation of chemotherapy in SCLC patients with IIPs made it possible to have a similar prognosis to that in those without IIPs.
We reported that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor re-administration (TKI-R) might be salvage therapy in patients with advanced non-small cell lung cancer after ...recovery from EGFR-TKI-induced interstitial lung disease (ILD). Here we retrospectively evaluated whether chemotherapy re-administration (CT-R) was effective in patients after chemotherapy-induced ILD. After providing their informed consent due to the risk of severe ILD, five patients received CT-R and six received TKI-R with oral administration of 0.5 mg/kg prednisolone. The overall survival (OS) from the occurrence of drug-induced ILD was shorter in CT-R cases than that in TKI-R cases (7.3 months vs. 25.4 months, p=0.003). The median duration of OS, however, was 7.3 months in cases with CT-R and 1.9 months in cases without CT-R. Multivariate analysis showed that CT-R as well as TKI-R tended to reduce the risk of mortality. CT-R might be salvage therapy in such patients, although the benefit of CT-R was smaller than that of TKI-R.
We retrospectively evaluated whether the ratio KL-6 to SLX in serum (K/S ratio) before chemotherapy was a predictor for the occurrence of drug-induced interstitial lung disease (D-ILD) in lung cancer ...patients with idiopathic interstitial pneumonias (IIPs). D-ILD occurred in 8 of 20 IIPs-positive cases and in 14 of 100 IIPs-negative cases (40 vs. 14%, p = .015). In IIPs-positive cases, the high K/S ratio (>20) before first-line chemotherapy had a tendency to increase the risk of D-ILD (p = .085). Serum K/S ratio may be a useful predictor for the occurrence of D-ILD in lung cancer patients with IIPs.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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