Here are my thoughts and guidance:
The Classes of New Options
Given your IBC and TNBC tumor biology and your clinical (treatment) history to date, these are some promising options to explore:
(1) Liposomal doxorubicin/LD (pegylated: Doxil, Caelyx; non-pegylated: Myocet). Anthracyclines remain, along with taxanes, one of the most active classes for IBC and TNBC, and anthracycline rechallenge appears to be unproblematic in it follows one year or more after initial exposure and this would be with the new generation liposomal anthracyclines, not the standard agents. (Your sole anthracycline exposure appears to have been back in 2009). LD is often combined with cyclophosphamide (Cytoxan) to yield LD-C but it can also be coupled with any of the third generation agents (LD-V with vinorelbine is one possible option).
(2) Docetaxel (Taxotere) - so far you have only been exposed to paclitaxel-based agents, namely paclitaxel (Taxol) itself, and nab-paclitaxel (Abraxane), and docetaxel with a distinct clinical profile can sometimes be highly effective independent of previous taxane exposure. It is exceptionally versatile and It can be combined with one of the third generation chemotherapeutics, in your case either gemcitabine (Gemzar) or vinorelbine (Navelbine) to yield either GT or VT (T=docetaxel) or with an anthracycline (epirubicin or liposomal doxorubicin, to yield either ET or LD-T), or with a platinum (either carboplatin or cisplatin), to yield PT. And given your previous exposure to carboplatin, a PT regimen if elected should be cisplatin + docetaxel.
(3) Vinorelbine (Navelbine) - you are chemonaive to this effective and well-tolerated agent, and it can be enhanced with the docetaxel into the well-evidenced VT regimen, or with cisplatin (VP regimen), or liposomal doxorubicin (V-LD).
(4) Enhanced CMF - this is gaining favor in the treatment of TNBC (Cliff Hudis at Memorial Sloan-Kettering being a big fan) and can often be surprisingly effective, especially when enhanced with an anthracycline like epirubicin (called the E-CMF regimen).
(5) Metronomic Capecitabine (Xeloda) - called metro-X, this is an effective regimen that minimizes adverse effects by low-dosing (1500 mg flat-dose (not BSA, or body surface area)), allowing it to then be combined with an anthracycline, a taxane (into metro-XT when docetaxel is used), a third generation agent (XV when vinorelbine is used), or a platinum like cisplatin (XP regimen). And studies have shown that it can be rechallenged after previous exposure to standard-dose capecitabine and still be effective, and at a metronomic level, it is unlikely hypotension would emerge).
One Possible Lineup, and Some Suggestions
- docetaxel with vinorelbine (VT) or
- docetaxel with cisplatin (PT), or
- vinorelbine plus cisplatin (VP), or
- liposomal doxorubicin plus docetaxel (LD-T), or
- liposomal doxorubicin plus cyclophosphamide (LD-C), or
- enhanced CMF (E-CMF)
- metronomic XT (metro-XT) using metronomic capecitabine + docetaxel, or
- metronomic XT (metro-XV) using metronomic capecitabine + vinorelbine, or
- metronomic XP (metro-XP) using metronomic capecitabine + cisplatin), or
may be the more promising ones to explore.
- that the first six are unique in combining two agents both of which you are naive to, and
- those of these which use cisplatin may serve double duty, both for systemic disease and also for activity against skin mets, as I discuss below.
- of course, any capecitabine rechallenge should be under close hypotension monitoring;
- eribulin may still be found effective, depending on what response on scans, and on your marker levels, indicate;
- gemcitabine (Gemzar) may still be a fallback option, under a triple regimen like the famous GET (gemcitabine + epirubicin + docetaxel) - it may simply not have been optimally deployed in combination with carboplatin that was used.
Skin Mets (Cutaneous Metastases)
Breast oncologists remain with no wide consensus on treatment of cutaneous (skin) metastases (regardless of location) from breast cancer, with one group favoring direct cutaneous mets treatment done concurrently with other systemic therapy, the other group favoring an indirect approach, reasoning that standard systemic therapy itself should work on the cutaneous mets along with any other breast cancer involvement. But as to direct therapy, there are these progressive options:
- Local Therapy for Skin Mets
(1) local therapy with a 6% solution of miltefosine (Miltex, Impavido) - this is not easily available in the U.S. but possible it can be prescribed off-label.
(2) photodynamic therapy (PDT), which has been used in the treatment of cutaneous metastasis of breast cancer with complete response rates ranging from 13.5% to 40% in candidates exhibiting only small volume disease.
(3) imiquimod (Aldara), based on a case study from Ulrich Hengge and colleagues in Germany; unfortunately, few breast oncologists are familiar with this specialized option [there is a recruiting clinical trial of imiquimod at the Fred Hutchinson Cancer Research Center in Seattle (Topical Imiquimod and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Breast Cancer), using imiquimod concurrently with nab-paclitaxel (Abraxane), but given progression on Abraxane, this is not an optimal choice].
Less common are these interventions:
(4) electrochemotherapy (ECT) with cisplatin, typically used in skin mets from breast cancer,
(5) pulsed irradiation / brachytherapy.
- Systemic Therapy for Skin Mets
The indirect approach, on the other hand, is via systemic therapy in general (endocrine and/or chemotherapy). If the mets are a special form called carcinoma erysipeloides, a cisplatin + 5-FU (called CDDP-F) regimen is used based on some early successes [Hinrichs and colleagues, Br J Dermatol 1999]. But for hormone-negative disease, including TNBC, the most widespread approach to skin metastases is indirect management through optimal systemic therapy for TNBC itself. As to skin-met-specific systemic agents, the data is sparse but I consider both:
(1) capecitabine (Xeloda) based on the case series of Kostandinos Sideras and colleagues at Mayo), and in your case a metronomic schedule would be safest, and
(2) cisplatin based on the retrospective review from Uger Coşkun and colleagues at Gazi University in Turkey,
as attractive, given that both of these are also highly active in TNBC disease, and my guidance typically is to try them in that order.
As you can see we have a broad spectrum of potential options to pursue with data to suggest efficacy in TNBC and many also effective in IBC, and there are as I show several distinct options for addressing the skin mets locally, although here certain systemic agents I identify may play double duty. All of these should be explored candidly with your oncologist, and you may also want to seek a second opinion.
Best fortune to you.
Breast Cancer Watch