What is the documentation of the usage of Gemzar in the treatment of lung adenocarcinoma?/nA patien

Fråga: What is the documentation of the usage of Gemzar in the treatment of lung adenocarcinoma?

A patient with lung adenocarcinoma is planned to receive Gemzar (gemcitabine) treatment. According to FASS the indication of Gemzar is adenocarcinom in pancreas.

Sammanfattning: Three of four phase II clinical trials of Gemzar in the treatment of non-small cell lung cancer (NSCLC) showed a response rate of about 20 per cent. The major adverse events seen during the treatment were hematologic, hepatic and renal toxicity. Hair loss was uncommon. Although Gemzar is not yet formally indicated for the treatment of NSCLC, the drug seems already to be used in practice for this indication.

Svar: Gemzar (gemcitabine) is a novel nucleoside analogue which was registered in Sweden in 1995 as a cytostatic with an indication of local advanced or metastatic adenocarcinoma in pancreas. At present Gemzar is not formally indicated for the treatment of non-small cell lung cancer (NSCLC), although an application for this indication has been sent to FDA (1).

Results of four phase II clinical trials are available internationally for 361 patients totally (2-5). Based on phase I studies the drug was administered as a 30 minute infusion once a week for three weeks, followed by a week of rest. The starting doses were 800-1250 mg/m(2)/wk x3 in the phase II clinical trials. The included patients aged 23-78 years with a majority of male patients and had stage IIIa, IIIb and IV disease. The majority of cancer types was adeno or squamous cells in the studies.

Three of the four clinical trials showed a tumor response rate of approximately 20 per cent (3,4,5) (response: a decrease of 50 per cent or more in the total tumor size of the measured lesions, determined by two observations not less than four weeks apart, and the appearance of no new lesions or progression of any lesion = partial response; or the disappearance of all known disease, determined by two observations not less than four weeks apart = complete response). One trial (cf 2) had a response rate of only 3.2 per cent (one out of 31 patients). Compared with the other three trials, there was in this study a higher percentage of patients who had received previous radiotherapy, an older patient population, a smaller number of patients included, a lower starting dose and a lower median effective patient dose. No significant relationship has been found between age and overall response rates (cf 2). Males had a slightly lower response rate (17.5 per cent, 43/246 patients) than females (23.5 per cent, 20/85 patients) but this was not statistically significant. Interestingly, the clearance of Gemzar was 20-40 per cent lower in women than in men (cf 2), which may result in higher plasma concentrations of Gemzar in women. However, the manufacturer does not suggest that lower doses need to be given to women because of the wide therapeutic index.

A few patient benefits have also been shown in these trials, for example improvements of performance status, body weight, analgesic use and disease-related symptoms such as hemoptysis (63 per cent), cough (44 per cent), somnolence (40 per cent) etc.

Adverse event data were derived from seven European phase II studies (n = 439) or from all phase II data (n = 790) collected from patients who received at least one dose of Gemzar 800-1250 mg/m(2). Hematologic toxicity included 6.4 per cent grade 3 anemia (6.5-7.9 gram/100 ml) and 0.9 per cent grade 4 anemia (<6.5 gram/100 ml); leukopenia grade 3 (1.0-1.9) 8.1 per cent and grade 4 (1.0) 0.5 per cent; neutropenia 18.7 per cent of grade 3 and 5.17 per cent of grade 4; platelet toxicity in 3.7 per cent grade 3 (25-49000 mm(3)) and 1.0 per cent grade 4 (< 25000/mm(3)). Less than one per cent of the patients discontinued treatment because of these adverse effects.

Less than 10 per cent of the patients had grade 3 or 4 abnormalities in liver enzyme levels and 0.5 per cent discontinued treatment due to these adverse events. Mild proteinuria and hematuria were reported in about one half of the patients and renal failure in 0.6 per cent. Approximately 20 per cent of the patients experienced severe nausea and vomiting, but rarely dose-limiting. Hair loss occurred in 0.5 per cent (grade 3). Other side effects were dyspnea (1.8 per cent); rash (25 per cent), flu-like symptoms (20 per cent) and edema (28 per cent).

Gemzar has been used at Huddinge Hospital in the treatment of NSCLC in relatively young patients with good general conditions, according to the dosing recommendations of the manufacturer (6). 1 Personal communication with Solveig Eklöf, Eli Lilly Sweden AB 2 Gemzar NSCLC (non-small cell lung cancer) monograph 1995; Eli Lilly and company 3 Andersson H, Lund B, Bach F, Thatcher N, Walling J, Hansen HH: Single-agent activity of weekly gemcitabine in advanced non-small-cell lung cancer: a phase II study. J Clin Oncol 1994; 12: 1821-1826 4 Abratt R, Bezwoda W, Falkson G et al: Efficacy and safety profile of gemcitabine in non-small cell lung cancer. A phase II study. J Clin Oncol 1994; 12: 1535-1540 5 Gatzemeier U, Shepherd FA, Chevalier T Le, Weynants P, Cottier B, Groen HJM, Rosso R, Mattson K, Cortes-Funes H, Tonato M, Burkes RL, Gottfried M, Voi M: Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study. Eur J Cancer 1996; 32A: 243-248 6 Personal communication with Dr Katarina Svartengren, Lungkliniken, Huddinge hospital