what to do about stubborn skin mets?
 

Since I was on kadcyla in june , the rash is now almost all gone. I will have a scan soon to find out how my chestwall nodes have responded hopefully a good response! However 3 new lesions have popped up and I am meeting with a surgeon this thursday. I am quite sure at least one of them is skin mets as they have all grown in size, become more red. I have had 3 types of chemo and it is getting very frustrating for me as I keep falling off the horse. I remember barbara in arizona had same issue with stubborn skin mets and she had radiation and now is on perjeta. Does anyone know what kind of radiation she had or anyone who had similar experience? Thanks

Re: what to do about stubborn skin mets?
 

Don't know if this would be helpful, but i remembered posting it before:

07-07-2012, 04:23 PM #1
Lani
Senior Member


already approved topical treatment effective vs skin mets


article did not mention her2 status of any of the involved patients, however

Clin Cancer Res. 2012 Jul 5. [Epub ahead of print]
Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.
Adams S, Kozhaya L, Martiniuk F, Meng TC, Chiriboga L, Liebes L, Hochman T, Shuman N, Axelrod D, Speyer JL, Novik Y, Tiersten A, Goldberg JD, Formenti SC, Bhardwaj N, Unutmaz D, Demaria S.
Source
Medicine, NYU School of Medicine.
Abstract
PURPOSE:
Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local anti-tumor immunity and induces the regression of breast cancer skin metastases.
EXPERIMENTAL DESIGN:
A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 days/week for 8 weeks. Safety and immunological correlates were secondary objectives.
RESULTS:
Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1-2 transient local and systemic side effects consistent with imiquimod's immunomodulatory effects. Two patients achieved a partial response (20%; 95% CI 3% - 56%). Responders showed histological tumor regression with evidence of an immune-mediated response, demonstrated by changes in the tumor lymphocytic infiltrate and locally produced cytokines.
CONCLUSIONS:
Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a pro-immunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest even superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve anti-tumor immune and clinical responses.
PMID: 22767669

Re: what to do about stubborn skin mets?
 

No good advice to offer her Yanyan but try doing a search on this site as many members have battled skin mets, holding good thoughts for you.

Re: what to do about stubborn skin mets?
 

Have you tried Xeloda cream? I have no experience but I know others who have tried it to keep things in control.

Re: what to do about stubborn skin mets?
 

Barb has had several spots pop up in the last three years. They dont seem to respond to any of the combinations shes been on. The only thing that has worked has been electron treatments which arent as invasive as full blown radiation. But they reappear in another area. Its like they are chasing the mets to another spot. Shes been on Herceptin/Perjeta and Taxotere since January successfully. There was a clinical trial in Washington state using Aldera cream along with a chemo but they wanted us to fly clear across the country and the wouldnt consider Barb because one spot was too severe, actually an open sore. The Electron chased it away. Hope this helps.

Re: what to do about stubborn skin mets?
 

Aldara cream and imiquimod are one and the same. Glad to hear about the clinical trial.

a quick google produced:

San Antonio Breast Cancer Symposium, 2011

Imiquimod/Abraxane Combo Effective for Skin Mets

By: BRUCE JANCIN, Oncology Report Digital Network

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m2 on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

as well as mention of the Aldara only trial @ NYU :


Toll-like Receptor (TLR) 7 Agonist and Radiotherapy for Breast Cancer With Skin Metastases
This study is currently recruiting participants.
Verified April 2013 by New York University School of Medicine
Sponsor:
New York University School of Medicine
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01421017
First received: August 17, 2011
Last updated: April 30, 2013
Last verified: April 2013
History of Changes
Full Text View Tabular ViewNo Study Results PostedDisclaimerHow to Read a Study Record
Purpose
The cell killing and immunostimulatory properties of two local treatment modalities, radiotherapy (RT) and Imiquimod (IMQ), may generate an effective immune response and lead to systemic control of breast cancer after local treatment of the cancer on the skin spread from the breast (skin metastases). This study is to find an optimal dose of IMQ in the first part and test the effectiveness of the combination treatment of RT and IMQ in patients with skin metastases from breast cancer in the second part.


Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
Recurrent Breast Cancer
Radiation: Radiation
Drug: Imiquimod
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of TLR7 Agonist Imiquimod and Radiotherapy in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Imiquimod
U.S. FDA Resources

Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
systemic tumor response rates (CR+PR) at the time of best overall response (Ph II) [ Time Frame: 9 weeks from the strat of the treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
local tumor response rates (CCR+PR) at best overall response (Ph II) [ Time Frame: 9 weeks from the start of the treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: August 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMQ+RT
At trial entry, all skin metastases will be divided into two areas (A) and (B) for differential treatment. Area A will receive IMQ + RT while area B will only receive IMQ. The size and location of cutaneous metastases for RT (area A) will be chosen by the radiation oncologist, to assure avoidance of overtreatment by radiation in pre-irradiated patients. All cutaneous metastases outside of area A will be included in area B.
Radiation: Radiation
Radiotherapy will be administered to Area A at a dose of 6 Gy given at five fractions on days 1, 3, 5, 8 and 10 (M-W-F-M-W) during a 8-week treatment cycle. All patients may continue to receive additional cycles (same schedule, RT given to a different cutaneous area, which may comprise all the prior area B), provided that patients wish to continue, are without clinically significant progression and further treatment may be beneficial in the opinion of the investigator
Drug: Imiquimod
Treatment with topical imiquimod 5% to all skin metastases (Areas A and B) starts the evening after the first radiation dose (day 1). IMQ treatment is given 5 days/week or Days 1, 3, 5/week for a total of 8 weeks (=1 cycle). The treatment dose is determined by tumor area: One single-use packet of imiquimod 5% (250 mg cream) per day is used for tumors <100cm^2, an additional package/d is added for each additional 100cm^2 area, not to exceed 6 packets/d. Patients self-apply a thin layer of IMQ 5% topically in the evening and wash it off the next morning (6-10 hours after initial application) with mild soap and water to remove any residual cream.
Other Name: ALDARA

Detailed Description:
This is a single arm, open label Phase I/II clinical trial to treat breast cancer with skin metastases (chest wall or other sites).

A brief Phase I part is conducted, to allow dose optimization in the event of unanticipated adverse events (3-3 design). In the Phase II part, efficacy is the primary endpoint. Twenty five patients will be enrolled to Phase II.

Eligibility

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Female
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Patients with biopsy-confirmed breast cancer.
Patients with measurable skin metastases and distant, measurable metastases (outside of skin) by RECIST. For patients without distant measurable metastases, an area of the skin metastases designated to not receive local therapy can be substituted.
Age >= 18 years.
ECOG performance status 0-2.
Patients must agree to tumor FNA required by protocol.
Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no CR or PR) on that regimen for >= 8 weeks as assessed by the investigator.
Patients must have adequate organ and bone marrow function as defined below:
absolute neutrophil count >= 1,300/microliter
hemoglobin >= 9.0 grams/deciliter
platelets >= 75,000/microliter
total bilirubin =< 1.5 X institutional upper limit of normal
AST =< 2.5 X institutional upper limit of normal
ALT < 2.5 X institutional upper limit of normal
creatinine =< 1.5 X institutional upper limit of normal
Informed consent.
Exclusion Criteria:

Brain metastases unless resected or irradiated and stable >= 4 weeks.
Concurrent treatment with other investigational agents.
Patients who have received any local therapy (radiotherapy, high-potency corticosteroids, intralesional therapy, laser therapy or surgery) other than biopsy to the target area within 4 weeks prior to first dosing of study agent.
Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.
Patients with an uncontrolled bleeding disorder.
Patients who will be therapeutically anticoagulated with heparins or coumadin at the time of the biopsy (they are eligible if anticoagulation can be held prior to biopsy as per investigator). Patients on aspirin and other platelet agents are eligible.
Patients with known immunodeficiency or receiving immunosuppressive therapies.
History of allergic reactions to imiquimod or its excipients.
Uncontrolled intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnancy or lactation.
Women of childbearing potential not using a medically acceptable means of contraception.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01421017

Contacts
Contact: Sylvia Adams, MD 212-263-6485 sylvia.adams@nyumc.org
Contact: Maria Fenton-Kerimian, NP 212-731-5035 maria.fenton-kerimian@nyumc.org

Locations
United States, New York
New York University Medical Center Recruiting
New York, New York, United States, 10016
Principal Investigator: Silvia Formenti, MD
Sub-Investigator: Amy Tiersten, MD
Sub-Investigator: Yelena Novik, MD
Sub-Investigator: James Speyer, MD
Sub-Investigator: Franco Muggia, MD
Sub-Investigator: Ruth Oratz, MD
Sub-Investigator: Stella Lymberis, MD
Sub-Investigator: Nelly Huppert, MD
Principal Investigator: Sylvia Adams, MD
Sponsors and Collaborators
New York University School of Medicine
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sylvia Adams, MD New York University School of Medicine
More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01421017 History of Changes
Other Study ID Numbers: NYU 11-00598, 1R01CA161891-01
Study First Received: August 17, 2011
Last Updated: April 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
radiation therapy
combination therapy
immunotherapy
immune response modifier
immunostimulatory
immunomodulator

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on October 24, 2013

Phase I/II study of TLR7 agonist imiquimod and radiotherapy in Breast Cancer Patients with Chest Wall Recurrence or Skin Metastases
The cell killing and immunostimulatory properties of two local treatment modalities, radiotherapy (RT) and Imiquimod (IMQ), may generate an effective immune response and lead to systemic control of breast cancer after local treatment of the cancer on the skin spread from the breast (skin metastases). This study is to find an optimal dose of IMQ in the first part and test the effectiveness of the combination treatment of RT and IMQ in patients with skin metastases from breast cancer in the second part

Learn more about this clinical trial at cancer.gov.

Contact
Sylvia Adams, MD
212-263-4432
sylvia.adams@nyumc.org

Maria Fenton-Kerimian, APN-bc, OCN
212-731-5035
maria.fenton-kerimian@nyumc.org

Re: what to do about stubborn skin mets?
 

just came across this :

Tumori. 2013 May-Jun;99(3):127e-30e. doi: 10.1700/1334.14821.
Unusual long-lasting cutaneous complete response to lapatinib and capecitabine in a heavily pretreated HER2-positive plurimetastatic breast cancer patient.
Pizzuti L, Sergi D, Barba M, Vici P.
Abstract
Lapatinib, in combination with capecitabine, has shown clinical activity in both first-line and refractory disease in patients with HER2-positive advanced breast cancer. Herein we describe the case of a plurimetastatic, heavily pretreated, HER2-positive breast cancer patient who experienced multiple cutaneous metastases successfully treated with lapatinib and capecitabine. An early complete response was obtained on all skin lesions, and no evidence of disease progression at other metastatic sites was observed for 22 months. The treatment was well tolerated, without dose-reductions or delays. In advanced breast cancer patients with skin metastases overexpressing HER2, previously treated with anthracyclines, taxanes and trastuzumab, lapatinib and capecitabine may represent a very active, safe and well-tolerated treatment option.
PMID: 24158082