Effects of para-toluenesulfonamide intratumoral injection on pulmonary adenoid cystic carcinoma complicating with severe central airway obstruction: a 5-year follow-up study

Abstract

Pulmonary adenoid cystic carcinoma (ACC) is a rare type of non-small cell lung carcinoma that may develop life-threatening severe malignant airway obstruction (SMAO). Currently, limited therapeutic approaches exist for ACC-SMAO. We investigated the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection for ACC-SMAO. In this phase III, multicenter, non-randomized, single-arm, openlabel trial, we recruited eight hospitalized patients with ACC-SMAO between October 2009 and January 2011. Within the first year, patients received PTS injection for 2-3 sessions weekly, with 2 weeks as a single course. Pre-and post-treatment assessments, including vital sign assessment, dyspnea index, chest computed tomography (CT), were performed shortly before PTS injection and at day 30 post-treatment. We extended the observation to 5 years to determine overall survival. The primary endpoint was the CT-assessed airway objective response rate (ORR) at day 30. The key secondary endpoint was the overall survival (OS) at 5 years post-treatment. At baseline, mean airway tumor cross-sectional area was 153.3 mm 2 (n=8), and the mean airway obstruction rate was 86.1%. The airway ORR reached 100% (33.3% complete remission and 66.7% partial remission). PTS treatment reduced the airway tumor size from 158.2 to 22.7 mm 2 and the average airway obstruction rate decreased from 83.1% to 14.4% (n=6). The 5-year overall survival rate was 50.0%. Median survival duration was 4.98 years (range, 1.39-5.00 years). Four patients (50.0%) had stable disease. Compared with baseline dyspnea index, the transitional dyspnea index increased significantly at 30 days after treatment (mean difference: 5.40; 95% CI, 0.31-10.49; P<0.05). Adverse events were reported in 75% of patients (n=6), of whom 33.3% (n=2) and 66.7% (n=4) were rated as mild and moderate, respectively. No SAE was reported. In conclusion, PTS could rapidly debulk ACC-SMAO, resulting in considerable improvement of five-year survival rate.

Bronchoscopic intratumoural therapies for non-small cell lung cancer

“…The side effect profile was otherwise tolerable and the study confirmed the anti-tumour effect of PTS in NSCLC. A 5-year follow up study analysing a subset of these patients with adenoid cystic carcinoma of the lung suggested similar safety and clinical benefits of intratumoural PTS [32].…”

“…Since then, many different experimental agents have been delivered to lung tumours via transbronchial needle injection (TBNI) including chemotherapy [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], gene therapies [35][36][37][38][39][40][41][42][43][44], and other immune adjuvants [13,14,45,46] (see table 1). These studies have established feasibility of local injection, and side effects have overall been minimal.…”

“…Endobronchial intratumoural chemotherapy Endobronchial intratumoural chemotherapy (EITC) has been reported by multiple investigators since 1982 [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Agents delivered by endobronchial injection include 99.5% ethanol, cisplatin, 5-fluorouracil, methotrexate, bleomycin and others (see table 1).…”

Effects of Para-Toluenesulfonamide on Canine Melanoma Xenotransplants in a BALB/c Nude Mouse Model

“…The dosage of cisplatin used here was based on studies investigating how this drug affects apoptosis, invasion, metastasis, angiogenesis, and the growth signal mechanisms in canine melanomas implanted in mice [ 24 ]. We based the PTS dosage on the dose that is generally used to treat lung cancer [ 12 ], and the route of PTS administration was according to that reported in various studies [ 12 , 13 , 94 , 98 ]. We assessed the growth of the tumors every 7 days by measuring their largest and smallest diameters and calculated their volume according to the following formula: V = 0.5 × a × b 2 , where a and b are the largest and smallest diameters, respectively.…”

Autophagic Activation and Decrease of Plasma Membrane Cholesterol Contribute to Anticancer Activities in Non-Small Cell Lung Cancer

“…Para -toluenesulfonamide is a simple small molecule displaying both in vitro and in vivo anticancer activities in a variety of cancers including lung cancer, prostate cancer and tongue squamous cell carcinoma [ 13 , 14 , 15 ]. The clinical trials show that para -toluenesulfonamide displays efficient anti-tumor activity against advanced hepatocellular carcinoma and non-small cell lung cancer through a concurrent local injection therapy [ 16 , 17 , 18 , 19 ]. Recently, we have demonstrated that para -toluenesulfonamide is a potential anti-tumor agent which inhibits both the Akt-dependent and -independent mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K) pathways in prostate cancers, and the disturbance of lipid raft and cholesterol contents also are involved in the para -toluenesulfonamide-mediated mechanism [ 15 ].…”