Management of rash to erlotinib (E) and cetuximab (C): Results from the SERIES (Skin and Eye Reactions to Inhibitors of EGFR and kinaseS) clinic algorithm

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19556-19556
Author(s):  
N. V. Martin ◽  
V. Pacifico ◽  
S. E. Lai ◽  
A. Rademaker ◽  
S. Ortiz ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Calcineurin Inhibitors ◽  
Complete Response ◽  
Dose Modification ◽  
Management Algorithm ◽  
Topical Calcineurin Inhibitors ◽  
Best Response ◽  
Epidermal Growth ◽  
Intervention Trials ◽  
Rash Management

19556 Background: Rash develops in approximately 90% of patients (pts) treated with epidermal growth factor receptor inhibitors (EGFRIs) E and C, leading to significant physical/psychosocial discomfort and inconsistent therapy. This study characterizes outcomes of a rash management algorithm developed in the multidisciplinary dermatology-oncology SERIES clinic. Methods: Retrospective chart analysis was performed of pts with E and C rashes (n=45) who were treated with: oral tetracyclines (doxycycline or minocycline) bid and topical calcineurin inhibitors (pimecrolimus/ tacrolimus) or corticosteroids bid. After a baseline visit, pts were assessed at 2–4 week intervals and CTC graded (G). Management data, skin biopsies and photographs were evaluated. Response was defined as: Complete Response (CR) = severity decrease (decr) by 2G, Partial Response (PR) = 1G decr, Stable Disease (SD) = no G change, and Progressive Disease (PD) = increase by = 1G. Best response (BR) was defined as the patient’s best rash outcome at any point in time. Results: 43 out of 45 pts had evaluable data. Of 27 women and 16 men, mean age = 60 yrs (range 34–88), 60% received E and 40% C. For BR, 51% of patients had a CR, 42% had PR, 7% had SD, and 0% had PD. Age was related to BR (p=0.036), with median ages (in years) of 66, 57.5 and 48 for 22, 18 and 3 pts with CR, PR and SD respectively. BR was related to grade (p=0.045), with CR in 69% of G1 pts, 35% in G2 pts, and 54% in G3 pts. BR was not related to E or C (p=0.40). Dose modification was required in 8% (E) and 22% (C) and dose discontinuation in 0% (E) and 17% (C) pts. Conclusions: SERIES algorithm rash management demonstrates that combined oral tetracyclines, topical calcineurin inhibitors and corticosteroids result in improvement in a majority of subjects. The greater rate of dose modification/discontinuation with C supports the need for proactive/early intervention. Trials are underway to evaluate prophylactic therapies against rash to EGFRIs. No significant financial relationships to disclose.

scholarly journals Anthracycline-containing versus carboplatin-containing neoadjuvant chemotherapy in combination with trastuzumab for HER2-positive breast cancer: the neoCARH phase II randomized clinical trial

2021 ◽  
Vol 13 ◽  
pp. 175883592110090
Author(s):  
Hong-Fei Gao ◽  
Zhiyong Wu ◽  
Ying Lin ◽  
Xiang-Yang Song ◽  
Yin Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Growth Factor Receptor ◽  
Group Versus ◽  
Complete Response ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Background: Although dual blockade HER2-based neoadjuvant chemotherapy is associated with excellent outcomes for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pertuzumab is not available to all patients due to cost. The optimal neoadjuvant chemotherapy for HER2-positive breast cancer in the presence of a single HER2 blockade is unknown. This study aimed to compare the efficacy and safety of epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (EC-TH) with docetaxel/carboplatin/trastuzumab (TCH) neoadjuvant setting for HER2-positive breast cancer under the single HER2 blockade. Methods: Patients with stage II-IIIC HER2-positive breast cancer were randomly assigned to either eight cycles of EC-TH every 3 weeks during all chemotherapy cycles, or six cycles of TCH every 3 weeks. The primary endpoint was pathological complete response (pCR) (defined as the absence of invasive tumor cells in breast and axilla, ypT0/is ypN0). Results: From May 2017 to November 2019, 140 patients were randomly assigned, and 135 patients were ultimately found evaluable for the primary endpoint. The pCR was recorded in 25 of 67 patients [37.3%; 95% confidence interval (CI), 25.8–50.0] in the EC-TH group and in 38 of 68 patients (55.9%, 95% CI, 43.3–67.9) in the TCH group ( p = 0.032). The most common adverse events (AEs) were neutropenia in 24 of 67 (35.8%) patients in the EC-TH group versus 27 of 68 (39.7%) in the TCH group ( p = 0.642), anemia in 33 of 67 (49.3%) patients in the EC-TH group versus 34 of 68 (50.0%) in the TCH group ( p = 0.931), and thrombocytopenia in five of 67 (7.5%) patients in the EC-TH group versus 17 of 68 (25.0%) in the TCH group ( p = 0.006). Conclusion: For patients receiving the single HER2 blockade trastuzumab for HER2-positive breast cancer, TCH regimen might be a preferred neoadjuvant therapy. Trial registration: This trial was registered with ClinicalTrials.gov identifier: NCT03140553) on 2 May 2017.

scholarly journals Intratumoral Epidermal Growth Factor Receptor Antisense DNA Therapy in Head and Neck Cancer: First Human Application and Potential Antitumor Mechanisms

2009 ◽  
Vol 27 (8) ◽  
pp. 1235-1242 ◽  
Author(s):  
Stephen Y. Lai ◽  
Priya Koppikar ◽  
Sufi M. Thomas ◽  
Erin E. Childs ◽  
Ann Marie Egloff ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Head And Neck ◽  
Growth Factor Receptor ◽  
Maximum Tolerated Dose ◽  
Antitumor Effects ◽  
Best Response ◽  
Positron Emission ◽  
Epidermal Growth

Purpose Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. Patients and Methods Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 μg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. Results Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively). Conclusion Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects.

Drug-induced alterations in Mg2+ homoeostasis

2012 ◽  
Vol 123 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Anke L. Lameris ◽  
Leo A. Monnens ◽  
René J. Bindels ◽  
Joost G. J. Hoenderop
Keyword(s):  
Adverse Effects ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
Calcineurin Inhibitors ◽  
Drug Induced ◽  
Neuromuscular Abnormalities ◽  
Broad Variety ◽  
Epidermal Growth ◽  
High Doses ◽  
Insight Into

Magnesium (Mg2+) balance is tightly regulated by the concerted actions of the intestine, bone and kidneys. This balance can be disturbed by a broad variety of drugs. Diuretics, modulators of the EGFR (epidermal growth factor receptor), proton pump inhibitors, antimicrobials, calcineurin inhibitors and cytostatics may all cause hypomagnesaemia, potentially leading to tetany, seizures and cardiac arrhythmias. Conversely, high doses of Mg2+ salts, frequently administered as an antacid or a laxative, may lead to hypermagnesaemia causing various cardiovascular and neuromuscular abnormalities. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg2+ balance will indicate ways of prevention and treatment of these adverse effects and could potentially provide more insight into Mg2+ homoeostasis.

Trastuzumab emtansine: a game changer in HER2-positive early breast cancer

2020 ◽  
Vol 16 (32) ◽  
pp. 2595-2609
Author(s):  
Max S Mano
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Pathological Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Epidermal Growth ◽  
Game Changer

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer

2018 ◽  
Vol 36 (10) ◽  
pp. 968-974 ◽  
Author(s):  
Xavier Pivot ◽  
Igor Bondarenko ◽  
Zbigniew Nowecki ◽  
Mikhail Dvorkin ◽  
Ekaterina Trishkina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Adverse Event ◽  
Growth Factor ◽  
Response Rate ◽  
Pathologic Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Phase Iii ◽  
Epidermal Growth

Purpose This phase III study compared SB3, a trastuzumab (TRZ) biosimilar, with reference TRZ in patients with human epidermal growth factor receptor 2–positive early breast cancer in the neoadjuvant setting ( ClinicalTrials.gov identifier: NCT02149524). Patients and Methods Patients were randomly assigned to receive neoadjuvant SB3 or TRZ for eight cycles concurrently with chemotherapy (four cycles of docetaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide) followed by surgery, and then 10 cycles of adjuvant SB3 or TRZ. The primary objective was comparison of breast pathologic complete response (bpCR) rate in the per-protocol set; equivalence was declared if the 95% CI of the ratio was within 0.785 to 1.546 or the 95% CI of the difference was within ± 13%. Secondary end points included comparisons of total pathologic complete response rate, overall response rate, event-free survival, overall survival, safety, pharmacokinetics, and immunogenicity. Results Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95% CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively. Conclusion Equivalence for efficacy was demonstrated between SB3 and TRZ on the basis of the ratio of bpCR rates. Safety and immunogenicity were comparable.

The quantification of epidermal growth factor receptor (EGFR) in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7597-7597
Author(s):  
C. Camps ◽  
R. Sirera ◽  
M. Muñoz-Navarro ◽  
G. Lopez-Vivanco ◽  
G. Alonso ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Complete Response ◽  
Binding Domain ◽  
Response To Therapy ◽  
First Line Therapy ◽  
Lower Egfr ◽  
Epidermal Growth ◽  
Nsclc Patients

7597 Background: EGFR has an extracellular ligand-binding domain that can be proteolitically cleaved from the cell surface and can be accurately quantified in blood by ELISA. We have investigated the usefulness of plasma EGFR measurements as prognostic marker in advanced NSCLC. Methods: The cohort consisted in 329 patients (p) with advanced NSCLC that received first-line therapy with cisplatin and docetaxel. The concentration levels of the EGFR extracellular binding domain were determined by a sandwich quantitative ELISA in the baseline, before therapy. Results: Median age was 61, range [39–80], 84% males, 100% caucasian, 68% stage IIIB and 32% IV and 99% PS 0–1. The histological subtypes were: 31% squamous cell carcinoma, 49% adenocarcinoma, 15% large cell, and 5% undifferentiated. 181 p achieved complete response (CR), partial response (PR) or stable disease (SD) and 109 p progressive disease (PD). Median patient's plasma levels of EGFR were 32.4 ng/ml. There were not differences in p according to histology, site of metastasis and ECOG. There were differences in response to therapy; CR+PR+SD p presented median EGFR of 31.97 ng/ml [13.2–48.6] vs 30 ng/ml [16.9–46.8] in the PD group (p=0.024). Dividing the cohort in two sets according to EGFR median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with EGFR<32.4 ng/ml had a median TTP of 3.9 months (m) [3.3–4.6] while for EGFR>32.4 ng/ml was 4.7 m [4.0–5.4], (p=0.024). OS when EGFR<32.4 ng/ml was 6.9 m [5.9–7.8] and for EGFR>32.4 ng/ml was 9.1 m [8.2–10.1], (p=0.038). Conclusions: Patients with PD presented significantly lower levels of serum EGFR than those patients with CR+PR+SD. There is a relationship among lower EGFR concentration in serum with a worst prognosis in advanced NSCLC p in terms of TTP and OS. No significant financial relationships to disclose.

Treatment patterns and outcomes of acneiform skin eruptions from anti-epidermal growth factor receptor (EGFR) therapies for metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19547-e19547
Author(s):  
Bogdan Dascalu ◽  
Hagen F. Kennecke ◽  
Howard John Lim ◽  
Winson Y. Cheung
Keyword(s):  
Overall Survival ◽  
Prophylactic Treatment ◽  
Cox Regression ◽  
Growth Factor Receptor ◽  
Median Number ◽  
Treatment Patterns ◽  
Reactive Groups ◽  
Epidermal Growth ◽  
Number Of Treatment ◽  
Rash Management

e19547 Background: Use of anti-EGFR therapies, such as cetuximab (Cmab) and panitumumab (Pmab), is associated with acneiform eruptions. Because research suggests a correlation between rash severity and outcomes in unselected patients, concerns remain that prophylactic treatment of rash may interfere with anti-tumor activities of these drugs. Our aims were to 1) characterize the treatment patterns for rash due to Cmab and Pmab and 2) evaluate if a prophylactic vs reactive approach to rash management modifies outcomes. Methods: All patients diagnosed with wild-type K-ras mCRC from July 2009 to June 2011 in British Columbia, Canada and prescribed either Cmab or Pmab were reviewed to describe patterns of prophylactic (before rash) and reactive (after rash) use of antibiotics and steroid creams. Using Cox regression, the relationship between rash management and overall survival was characterized. Results: In total, 119 patients were analyzed: median age at diagnosis was 63 years, 61% were men, 34% received Cmab and 66% Pmab, and median number of anti-EGFR treatment was 9 cycles. Rash occurred in over 90% of patients. Among them, reactive was favored over prophylactic treatment (66 vs 34%). Older patients (60+ years) and those with ECOG 0/1 were more likely to receive prophylactic creams (44 vs 20%, p=0.01) and antibiotics (62 vs 12%, p=0.01), respectively. There were no further differences in rash management based on other patient or tumor characteristics (all p>0.05). Median OS was 7.0 months. The number of treatment cycles and overall survival were similar in both prophylactic and reactive groups (both p>0.05). In Cox regression, ECOG 2+ correlated with worse survival than ECOG 0/1 (HR for death 5.25 95% CI 2.01- 9.23, p<0.01). However, survival outcomes were statistically similar between patients prescribed antibiotics prophylactically vs. reactively (HR=1.10, 95% CI 0.43-2.80, p=0.85) and between patients given steroid creams prophylactically vs. reactively (HR=2.00, 95% CI 0.58-6.92, p=0.27). Conclusions: Prophylactic treatment of anti-EGFR related rash is associated with similar outcomes as compared to reactive rash treatment in mCRC patients.

Ca-15.3 antigen as predictor of response to EGFR inhibitors in patients with bronchiolo-alveolar carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18151-18151
Author(s):  
A. Bearz ◽  
R. Talamini ◽  
E. Vaccher ◽  
M. Spina ◽  
C. Simonelli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Marker ◽  
Growth Factor Receptor ◽  
Female Gender ◽  
Complete Response ◽  
Serum Levels ◽  
Egfr Inhibitors ◽  
First Line Therapy ◽  
Close Relationship ◽  
Epidermal Growth

18151 Background: Bronchiolo-alveolar carcinoma (BAC) is a subtype of non-small cell lung cancer (NSCLC). Incidence of pure BAC ranges between 2% and 5% of NSCLC although a BAC histotype may be present in up to 20%. There is no established treatment for BAC, although promising results have been achieved from the use of inhibitors of the Epidermal Growth Factor Receptor (EGFR). It has been demonstrated that there is a very close relationship between responsiveness to EGFR inhibitors Erlotinib and Gefitinib and some factors, including female gender; adenocarcinoma histotype, with BAC features; Asian origin; and never having smoked. No tumor marker has been validated in the diagnosis and follow-up of lung cancer. Ca 15–3 antigen serum levels are reported to be pathologically abnormal in adenocarcinoma of the lung, although it does not seem to be related to the EGFR pathway. We studied this tumor marker in relation with the treatment with EGFR inhibitors in patients affected by BAC. Methods: We collected data from 16 caucasian, female and never smoker pts with BAC. All pts received EGFR inhibitors as first-line therapy. In compliance with the EAP, dosage of Gefitinib and Erlotinib was 250 mg/day and 150 mg/day, respectively. Results: One (6%) pt had a complete response and 6 (38%) showed a partial response to EGFR inhibitors, 1 (6%) pt remained stable for 4 months, while 8 (50%) pts progressed. All 7 pts with normal Ca 15–3 levels before treatment with EGFR inhibitors’ achieved a partial or complete response, but the 8 pts with abnormal Ca 15–3 levels did not (p=0.0001). Among the responders we noticed an increase of Ca 15–3 serum levels at progression. In particular, 5 pts had an increase of Ca 15–3 serum levels up to normal value when their disease progressed; 2 pts have not progressed yet and Ca 15–3 serum levels remain normal. Conclusions: We suggest that Ca 15–3 levels may be a prognostic factor to predict the response to EGFR inhibitors in pts with BAC. We are studying its role in a larger population with BAC and in other NSCLC subtypes as well. No significant financial relationships to disclose.

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