Phase II trial of a 75-mg/m2 dose of docetaxel with prednisone premedication for patients with advanced non-small cell lung cancer

Abstract

Background. A prior Phase II study of a 100‐mg/m2 dose of docetaxel conducted at the Memorial Sloan‐Kettering Cancer Center (New York, NY) demonstrated a 38% response rate with grade 3 or 4 neutropenia in 76% of the patients and a grade 2 or greater rash or infusion‐related reaction in 41% and 34% of the patients, respectively. The current Phase II study sought to determine the activity of a 75‐mg/m2 dose of docetaxel to establish whether this lower dose, combined with prednisone, ameliorates toxicity. Methods. Twenty untreated patients with advanced non‐small cell lung cancer (NSCLC) received a 1‐hour 75‐mg/m2 dose of docetaxel every 21 days. Fifty milligrams of prednisone were administered twice the day before chemotherapy and once each of the next 3 days. Patients' disease‐related symptoms were assessed prospectively using the Lung Cancer Symptom Scale (LCSS). Results. All patients were assessable for response and toxicity. Five patients had a major objective response (25%; 95% confidence interval, 11‐50%). The median duration of response was 9.1 months. The projected 1‐year survival was 71%. Grade 3 or 4 neutropenia occurred in 70% of the patients. Grade 2 or greater rash and infusion‐related reactions decreased to 25% each. Analysis of the LCSS measurements found that six of nine component symptoms improved on Day 22, and all improved when baseline measurements were compared with the best value for each patient during the study. Conclusions. Docetaxel administered at a dose of 75 mg/m2 every 21 days shows significant antitumor activity in untreated patients with NSCLC. Neutropenia is comparable with that observed at a 100‐mg/m2 dose. The number of infusional reactions and rash decreased when docetaxel at this dose was administered with prednisone. Based on response rates observed in trials using a 100‐mg/m2 dose with similar degrees of neutropenia, a 100‐mg/m2 dose with steroid pretreatment is recommended future trials. Cancer 1995;75:968‐72.

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours

“…Based on these phase I studies, the recommended singleagent dose and schedule for docetaxel was 100 mg m-2 given as a 1-h infusion every 3 weeks. Phase II studies on docetaxel showed activity in breast cancer (Seidman et al, 1993;Ten Bokkel-Huinink et al, 1994;Trudeau et al, 1993;Valero et al, 1993;Chevallier et al, 1995), non-small-cell lung cancer (Cemy et al, 1994;Fossella et al, Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands 1995; Miller et al, 1995), head and neck cancer , gastric cancer (Sulkes et al, 1994), melanoma (Aamdal et al, 1994), soft tissue sarcoma (Van Hoesel et al, 1994) and pancreatic cancer (De Fomi et al, 1994). The most important side-effect was an early and short-lasting neutropenia, which in 20% of the patients was complicated by infection (Pronk et al, 1995).…”

Phase II Trial of Docetaxel in Asian Patients with Inoperable Stage III Non-Small Cell Lung Cancer

“…Dose reduction according to body surface area does not necessarily lead to less toxicity. In fact, one trial has shown that a reduction of dose to 75 mg/m 2 had little effect on the incidence or severity of neutropenia (21). This is not surprising considering the known wide interpatient variability of pharmacokinetics of most cytotoxics.…”

New Agents in the Management of Non-Small-Cell Lung Cancer

“…Investigators at Memorial Sloan-Kettering Cancer Center also evaluated a slightly lower dose of docetaxel (75 mg/m 2 ) in an attempt to lower toxicity. 53 In all studies, the principal toxicity proved to be myelosuppression, although rash and fluid retention were common. Hypersensitivity reactions or allergic reactions were also common but rarely precluded treatment.…”

“…However, investigators at Memorial Sloan-Kettering Cancer Center recommend using the higher docetaxel dose in future NSCLC studies. 53 This recommendation was made largely because the toxicity of the lower dose of docetaxel (75 mg/m 2 ) was comparable to that of the higher dose (100 mg/m 2 ) in their hands. Japanese investigators have found lower doses of 60 mg/m 2 yield response rates in breast cancer equivalent to that achieved with the higher docetaxel doses.…”