Etoposideversus etoposide plus high-dose cisplatin in the management of advanced non-small cell lung cancer: Results of a prospective randomized fonicap trial

Abstract

Two hundred sixteen patients with unresectable non-small cell lung carcinoma were randomly allocated to receive etoposide (120 mg/m2, days 1-3) either alone or in combination with high-dose cisplatin (60 mg/mz, days 1-2). The patients' distribution and characteristics were similar in the two treatment arms. The objective response rate for etoposide was 7% versus 25.8% for etoposide plus cisplatin ( P < 0.005). Median progression-free survival in etoposide arm was 3.5 months versus 5 months in the combination arm ( P = 0.43). The median survival time for etoposide was 6 months compared with 8 months for etoposide combined with cisplatin (P = 0.87). Significantly more nausea/vomiting (P < 0.005), serum creatinine elevation ( P < 0.0051, hearing loss and/or tinnitus ( P < 0.005), peripheral neuropathy ( P < 0.005), leukopenia ( P < 0.025), and anemia ( P < 0.005) occurred in the etoposide plus cisplatin arm. No statistically significant difference was recorded between the two arms in terms of performance status changes. In conclusion the addition of high-dose cisplatin to single-agent etoposide significantly increases the chance of obtaining tumor response in advanced non-small cell lung cancer at the cost of an increased toxicity without any significant long-term impact on survival and progression-free survival.

Ototoxic Adverse Drug Reactions: A Disproportionality Analysis Using the Italian Spontaneous Reporting Database

“…Moreover, in US post-marketing data about vinorelbine, hearing impairment has been reported (Food and Drug Administration, 2014). As far as etoposide was concerned, in a randomized trial, tinnitus and/or hearing loss was present in 24.5% of patients treated with etoposide and cisplatin versus 2.8% of patients in treatment with single-agent etoposide (Rosso et al, 1990). In the disproportionality analysis, we found a statistically significant ROR for drugs used in cardiovascular disorders (beta-blockers, plain ACE inhibitors, RAS-acting agents, selective Ca 2+ channel blockers, and alpha-blockers) but also for the single active substances (propafenone, doxazosin, metoprolol, bisoprolol, nebivolol, ramipril, irbesartan, losartan and diuretics, and hydrochlorothiazide and potassium-sparing agents).…”

Platinum drugs in the treatment of non-small-cell lung cancer

“…Comparisons between cisplatin containing double therapy and monotherapy with the non-platinum agent Results of trials comparing monotherapy with vindesine (Elliott et al, 1984;Einhorn et al, 1986), etoposide (Rosso et al, 1990), teniposide (Splinter et al, 1996), and vinorelbine (Depierre et al, 1994;Le Chevalier et al, 1994) with the respective agent combined with cisplatin showed consistently higher response rates in the combination therapy arm, but only about half showed a survival benefit for the combination (Table 2). Similarly, preliminary analysis of a multicenter phase III trial comparing docetaxel vs docetaxel plus cisplatin in patients with inoperable advanced and metastatic NSCLC showed no survival advantage but a significant improvement in objective response rate with combination therapy (Georgoulias et al, 2002; Table 2).…”

High dose tamoxifen plus cisplatin and etoposide in the treatment of patients with advanced, inoperable nonsmall cell lung carcinoma

“…Longeval and Klastersky used cisplatin and etoposide in 94 patients with advanced NSCLC: A 38% response rate and a median survival of 7.5 months were noted 23. The accumulated response rate of cisplatin and etoposide in 647 patients from 7 trials was 28% (20–30%) 24–30. The median survival times in these 7 studies ranged from 24.5 weeks to 32 weeks.…”