Abstract
Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m2/wk x 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m2/wk. However, increased severity of leucopenia (dose-limiting) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/ m2/wk. In all, 6 out of 11 patients experiencing WHO grade≥ 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in ≤ 5%. The good tolerability and the evidence of antitumor activity of GEM at doses ≥ 875 mg/m2/wk (1 CR and 3 PRs in 15 bladder cancer patients) encourage further phase II studies at much higher dose-levels (1,370 mg/m2) than previously suggested.
| Original language | English |
|---|---|
| Pages (from-to) | 111-119 |
| Number of pages | 9 |
| Journal | Investigational New Drugs |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jun 1994 |
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Keywords
- gemcitabine
- phase I study
- solid tumors
ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
Cite this
Weekly gemcitabine in advanced or metastatic solid tumors - A clinical phase I study. / Pollera, Camillo F.; Ceribelli, Anna; Creccon, Marcello; Calabresi, Federico.
In: Investigational New Drugs, Vol. 12, No. 2, 06.1994, p. 111-119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Weekly gemcitabine in advanced or metastatic solid tumors - A clinical phase I study
AU - Pollera, Camillo F.
AU - Ceribelli, Anna
AU - Creccon, Marcello
AU - Calabresi, Federico
PY - 1994/6
Y1 - 1994/6
N2 - Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m2/wk x 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m2/wk. However, increased severity of leucopenia (dose-limiting) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/ m2/wk. In all, 6 out of 11 patients experiencing WHO grade≥ 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in ≤ 5%. The good tolerability and the evidence of antitumor activity of GEM at doses ≥ 875 mg/m2/wk (1 CR and 3 PRs in 15 bladder cancer patients) encourage further phase II studies at much higher dose-levels (1,370 mg/m2) than previously suggested.
AB - Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m2/wk x 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m2/wk. However, increased severity of leucopenia (dose-limiting) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/ m2/wk. In all, 6 out of 11 patients experiencing WHO grade≥ 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in ≤ 5%. The good tolerability and the evidence of antitumor activity of GEM at doses ≥ 875 mg/m2/wk (1 CR and 3 PRs in 15 bladder cancer patients) encourage further phase II studies at much higher dose-levels (1,370 mg/m2) than previously suggested.
KW - gemcitabine
KW - phase I study
KW - solid tumors
UR - http://www.scopus.com/inward/record.url?scp=0027946936&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027946936&partnerID=8YFLogxK
U2 - 10.1007/BF00874440
DO - 10.1007/BF00874440
M3 - Article
C2 - 7860227
AN - SCOPUS:0027946936
VL - 12
SP - 111
EP - 119
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 2
ER -