Abstract
Background: Cetuximab is a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR). The recommended dosage is an initial load of 400 mg/m2 intravenously (IV) followed by a weekly maintenance dose of 250 mg/m2. It has been reported retrospectively that cetuximab efficacy was correlated with dose-related severity of skin rash. This study was prospectively designed to examine the safety and feasibility of escalating weekly doses of cetuximab, testing the hypothesis of the relationship of dose-dependent skin toxicity and efficacy. Methods: Four dose levels were tested: Cetuximab 400 mg/m2 IV loading dose and 250, 300, 350, 400 mg/m2 weekly IV maintenance. There was no intra-patient dose escalation. Standard dose limiting toxicity criteria were used. Rash was evaluated using two additional validated dermatology methods: global acne grading scale (GAGS) and acne lesion counting (ALC). Tumor specimens and blood samples were obtained for correlative analyses. Results: Twenty seven patients with solid tumors were enrolled: five head and neck, three pancreas, four gall bladder, two each of prostate, breast, colorectal, lung, and esophagus, and five others. Planned dose escalation was completed without reaching dose-limiting toxicity (DLT) or the maximum tolerated dose (MTD). The highest dose level was expanded to a total of 17 patients. Gr 3/4 toxicities included: lymphopenia (2), fatigue (2), and hypomagnesemia (2). One patient experienced a grade 3 rash (350 mg/m2). Sixty five percent of pts had a ≥ Gr 2 rash that was not dose dependent. In 22 evaluable patients, there was one partial response (PR) in a patient with cholangiocarcinoma (400 mg/m2) and seven patients had stable disease (SD). ALC and GAGS demonstrated no correlation with dose or response. Correlative studies evaluating k-ras, EGFR FISH status and immunologic correlatives were conducted on available tumor samples. Conclusions: Cetuximab administered at 400 mg/m2 IV as a loading dose with weekly maintenance dose of 400 mg/m2 is feasible and well tolerated. There was no direct correlation of the grade of rash with dose in this group of patients with heterogenous solid tumors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 680-687 |
| Number of pages | 8 |
| Journal | Investigational New Drugs |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 2011 |
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Keywords
- Acne lesion counting
- Acneiform rash
- Cetuximab
- Global acne grading scale
- Solid tumors
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Oncology
Cite this
Escalating weekly doses of cetuximab and correlation with skin toxicity : A phase I study. / Ho, Cheryl; Sangha, Randeep; Beckett, Laurel A; Tanaka, Michael; Lau, Derick H; Eisen, Daniel B; Burich, Rachel A.; Luciw, Paul A; Khan, Imran; Mack, Philip; Gandara, David R; Davies, Angela M.
In: Investigational New Drugs, Vol. 29, No. 4, 08.2011, p. 680-687.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Escalating weekly doses of cetuximab and correlation with skin toxicity
T2 - A phase I study
AU - Ho, Cheryl
AU - Sangha, Randeep
AU - Beckett, Laurel A
AU - Tanaka, Michael
AU - Lau, Derick H
AU - Eisen, Daniel B
AU - Burich, Rachel A.
AU - Luciw, Paul A
AU - Khan, Imran
AU - Mack, Philip
AU - Gandara, David R
AU - Davies, Angela M.
PY - 2011/8
Y1 - 2011/8
N2 - Background: Cetuximab is a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR). The recommended dosage is an initial load of 400 mg/m2 intravenously (IV) followed by a weekly maintenance dose of 250 mg/m2. It has been reported retrospectively that cetuximab efficacy was correlated with dose-related severity of skin rash. This study was prospectively designed to examine the safety and feasibility of escalating weekly doses of cetuximab, testing the hypothesis of the relationship of dose-dependent skin toxicity and efficacy. Methods: Four dose levels were tested: Cetuximab 400 mg/m2 IV loading dose and 250, 300, 350, 400 mg/m2 weekly IV maintenance. There was no intra-patient dose escalation. Standard dose limiting toxicity criteria were used. Rash was evaluated using two additional validated dermatology methods: global acne grading scale (GAGS) and acne lesion counting (ALC). Tumor specimens and blood samples were obtained for correlative analyses. Results: Twenty seven patients with solid tumors were enrolled: five head and neck, three pancreas, four gall bladder, two each of prostate, breast, colorectal, lung, and esophagus, and five others. Planned dose escalation was completed without reaching dose-limiting toxicity (DLT) or the maximum tolerated dose (MTD). The highest dose level was expanded to a total of 17 patients. Gr 3/4 toxicities included: lymphopenia (2), fatigue (2), and hypomagnesemia (2). One patient experienced a grade 3 rash (350 mg/m2). Sixty five percent of pts had a ≥ Gr 2 rash that was not dose dependent. In 22 evaluable patients, there was one partial response (PR) in a patient with cholangiocarcinoma (400 mg/m2) and seven patients had stable disease (SD). ALC and GAGS demonstrated no correlation with dose or response. Correlative studies evaluating k-ras, EGFR FISH status and immunologic correlatives were conducted on available tumor samples. Conclusions: Cetuximab administered at 400 mg/m2 IV as a loading dose with weekly maintenance dose of 400 mg/m2 is feasible and well tolerated. There was no direct correlation of the grade of rash with dose in this group of patients with heterogenous solid tumors.
AB - Background: Cetuximab is a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR). The recommended dosage is an initial load of 400 mg/m2 intravenously (IV) followed by a weekly maintenance dose of 250 mg/m2. It has been reported retrospectively that cetuximab efficacy was correlated with dose-related severity of skin rash. This study was prospectively designed to examine the safety and feasibility of escalating weekly doses of cetuximab, testing the hypothesis of the relationship of dose-dependent skin toxicity and efficacy. Methods: Four dose levels were tested: Cetuximab 400 mg/m2 IV loading dose and 250, 300, 350, 400 mg/m2 weekly IV maintenance. There was no intra-patient dose escalation. Standard dose limiting toxicity criteria were used. Rash was evaluated using two additional validated dermatology methods: global acne grading scale (GAGS) and acne lesion counting (ALC). Tumor specimens and blood samples were obtained for correlative analyses. Results: Twenty seven patients with solid tumors were enrolled: five head and neck, three pancreas, four gall bladder, two each of prostate, breast, colorectal, lung, and esophagus, and five others. Planned dose escalation was completed without reaching dose-limiting toxicity (DLT) or the maximum tolerated dose (MTD). The highest dose level was expanded to a total of 17 patients. Gr 3/4 toxicities included: lymphopenia (2), fatigue (2), and hypomagnesemia (2). One patient experienced a grade 3 rash (350 mg/m2). Sixty five percent of pts had a ≥ Gr 2 rash that was not dose dependent. In 22 evaluable patients, there was one partial response (PR) in a patient with cholangiocarcinoma (400 mg/m2) and seven patients had stable disease (SD). ALC and GAGS demonstrated no correlation with dose or response. Correlative studies evaluating k-ras, EGFR FISH status and immunologic correlatives were conducted on available tumor samples. Conclusions: Cetuximab administered at 400 mg/m2 IV as a loading dose with weekly maintenance dose of 400 mg/m2 is feasible and well tolerated. There was no direct correlation of the grade of rash with dose in this group of patients with heterogenous solid tumors.
KW - Acne lesion counting
KW - Acneiform rash
KW - Cetuximab
KW - Global acne grading scale
KW - Solid tumors
UR - http://www.scopus.com/inward/record.url?scp=79959697579&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959697579&partnerID=8YFLogxK
U2 - 10.1007/s10637-010-9396-4
DO - 10.1007/s10637-010-9396-4
M3 - Article
C2 - 20148348
AN - SCOPUS:79959697579
VL - 29
SP - 680
EP - 687
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 4
ER -