HonCode

Go Back   HER2 Support Group Forums > her2group
Register Gallery FAQ Members List Calendar Search Today's Posts Mark Forums Read

Reply
 
Thread Tools Display Modes
Old 04-25-2016, 03:25 PM   #1
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,778
Thumbs up for those with leptomeningeal metastasis--a case study with hope!!!!!

pulsatile very high dose lapatinib!!

Brief Report
Breast Cancer Research and Treatment
pp 1-2
First online: 22 April 2016
Bi-weekly very-high-dose lapatinib: an easy-to-use active option in HER-2-positive breast cancer patients with meningeal carcinomatosis
P. Lavaud , B. Rousseau, Z. Ajgal, J. Arrondeau, O. Huillard, J. Alexandre, A. Hulin, F. Goldwasser
10.1007/s10549-016-3798-8
Copyright information
The erbb2 gene, which encodes the growth factor receptor HER2, is amplified and overexpressed in 15–25 % of breast cancers, associated with poorer prognosis before the use of HER2 targeting agents. In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel significantly improved the median overall survival to 56.5 months [1]. Prolonged survival combined with high neurotropism of HER2-amplified tumors results in increasing incidence of leptomeningeal metastases. Due to very limited options, this situation represents an emerging issue. The prognosis of breast cancer patients with meningeal carcinomatosis is very poor with a reported median survival of 4.5 months with high-dose intrathecal methotrexate [2]. Of crucial importance, comparison of HER2 statuses in cerebrospinal fluid-derived tumor cells from patients with metastatic breast cancer with leptomeningeal carcinomatosis and corresponding archival primary tumors revealed a very concordance rate [3]. Furthermore, because of the high molecular weight of trastuzumab and pertuzumab, unable to cross the blood–brain barrier, leptomeninges may be a sanctuary for cancer cells to monoclonal antibodies. Consequently, meningeal metastases may result from a pharmacokinetic limitation to treatment delivery rather than from a molecular resistance to HER2 blockade. The pulsatile administration of high doses of tyrosine kinase inhibitors is a potential way to obtain a very high plasma maximal concentration, resulting in active concentrations in the leptomeninges [4]. Lapatinib, a reversible dual tyrosine kinase inhibitor of EGFR and HER2, is active in patients with HER2-positive metastatic breast cancer. Because it has a small molecular weight and is lipophilic, we hypothesized that very high doses of lapatinib may circumvent the sanctuary effect in case of HER2-positive breast cancer with leptomeningeal metastases.
We report the case of a 66-year-old woman who presented with a HER2-positive breast cancer with bone and liver synchronous metastases diagnosed in April 2012. Trastuzumab-based systemic chemotherapy resulted in a complete response of the liver. In April 2014, while being under trastuzumab and lapatinib, she presented severe headache, ataxia, and rapidly progressing dysarthria. The magnetic resonance imaging confirmed diffuse meningeal metastases. She was treated with high-dose lapatinib given once a day, twice a week, with plasma concentration monitoring. The dose was guided by clinical tolerance and efficacy with an initial dose of 5000, 6250 mg at the second intake, and 7500 mg (30 pills at once) at the third intake. The patient experienced grade 3 diarrhea lasting one day, the day after the first and third intakes. After the first administration, the headache disappeared within 2 days, and she recovered from both ataxia and dysarthria after 1 week of administration. Pre-cycle 2 and pre-cycle 3 through concentrations (Cmin) of lapatinib were 1041 and 1274 ng/ml, consistent with reported pharmacokinetic data and linear clearance of the high-dose lapatinib [5]. In August 2015, the patient is off therapy, alive and well, without neurological clinical manifestation, 16 months after the diagnosis of meningeal carcinomatosis. This encouraging clinical observation suggests that pulsatile lapatinib treatment may be considered as a more friendly alternative option to intrathecal treatments in patients with HER2-positive leptomeningeal metastases.
Compliance with ethical standard

Conflict of interest

The authors have declared no conflicts of interest.
References

1.
Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J, CLEOPATRA Study Group (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372(8):724–734
CrossRefPubMed
2.
Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, Laurence V, Livartowski A, Mignot L, Diéras V (2010) Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21(11):2183–2187
CrossRefPubMed
3.
Magbanua MJM, Melisko M, Roy R, Sosa EV, Hauranieh L, Kablanian A et al (2013) Molecular profiling of tumor cells in cerebrospinal fluid and matched primary tumors from metastatic breast cancer patients with leptomeningeal carcinomatosis. Cancer Res 73(23):7134–7143
CrossRefPubMed
4.
Cessot A, Blanchet B, Goldwasser F (2014) Erlotinib treatment of meningeal carcinomatosis in lung cancer: more is better. Ann Oncol 25(10):2093–2094
CrossRefPubMed
5.
Storniolo AM, Pegram MD, Overmoyer B, Silverman P, Peacock NW, Jones SF et al (2008) Phase I dose escalation and pharmacokinetic study of lapatinib in combination with trastuzumab in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 26(20):3317–3323
CrossRefPubMed
Copyright information

© Springer Science+Business Media New York 2016
Lani is offline   Reply With Quote
Old 04-27-2016, 08:27 PM   #2
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: for those with leptomeningeal metastasis--a case study with hope!!!!!

Wow. Very cool.
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 04-28-2016, 09:16 AM   #3
YoungMD
Member
 
Join Date: Apr 2016
Posts: 5
Re: for those with leptomeningeal metastasis--a case study with hope!!!!!

Holy moley, lapatinib is very hard on the bowel. But hopefully it can kill the LM mets.
YoungMD is offline   Reply With Quote
Old 05-22-2016, 03:58 AM   #4
Freakzilla
Senior Member
 
Join Date: Mar 2014
Posts: 55
Re: for those with leptomeningeal metastasis--a case study with hope!!!!!

This is great news
Freakzilla is offline   Reply With Quote
Reply

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is Off

Forum Jump


All times are GMT -7. The time now is 06:15 PM.


Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2024, vBulletin Solutions, Inc.
Copyright HER2 Support Group 2007 - 2021
free webpage hit counter