Rapid clinical and radiographic improvement after intrathecal trastuzumab and methotrexate in a patient with HER-2 positive leptomeningeal metastases

Figures & data

Figure 1. (a) Pre-treatment axial T1 weighted post-contrast MR image of the brain. The arrow points to enhancement caused by tumor deposits. (b) Post-treatment axial T1 weighted post-contrast MR image of the brain – indicates interval response to treatment.

Figure 2. (a) Pre-treatment sagittal T1 weighted post-contrast MR image of the spinal cord – note the diffuse enhancement surrounding the cord as indicated by the arrow. (b) Post-treatment sagittal T1 weighted post-contrast MR image of the spinal cord – improvement is noted as indicated by the arrow.

Figure 3. (a) Pre-treatment axial T1 weighted post-contrast MR image of the spinal cord – areas of leptomeningeal involvement are indicated by the arrow and are visible as an area of enhancement that encircles the spinal cord. In (b) improvement is noted and is indicated by the arrow.

Table I. Summary of intrathecal trastuzumab plus methotrexate case reports in breast cancer [7,9,13].

Reference	IT doses	Frequency of IT doses	Time on IT therapy	Time to response	Duration of response	Survival	Other IT therapy^1	Other systemic therapy^1
Laufman, 2001 [7]	Tras 5–20 mg^2, Mtx 15 mg	5–11 days	1.9 months	4.3 weeks	1 month	2.2 months	Thio 15 mg	Tras Pac Dex
Stemmler, 2008 [9]	Tras 20 mg, Mtx 12 mg	3–6 days	0.5 months	<2 weeks	∼1 month	1.3 months	None	Tras
Ferrario, 2009 [13]	Tras 20–50 mg^2, Mtx 10 mg	Initially weekly; then every 3 weeks	>24 months^3	Clinical: several months CSF: <1 week	CNS response for >24 months	>24 months^3	Thio 10–12 mg	Tras Pld Vin Pac
Current Report	Tras 20 mg, Mtx 6 mg	Initially twice per week; then weekly	2.7 months	3 weeks	2.7 months	5 months	None	Lap

CIT, intrathecal; CNS, central nervous system; Dex, dexamethasone; Lap, lapatinib; Mtx, methotrexate; Pac, paclitaxel; Pld, pegylated liposomal doxorubicin; SF, cerebrospinal fluid; Thio, thiotepa; Tras, trastuzumab; Vin, vinorelbine.

¹Other IT or systemic therapy was administered concurrently with IT trastuzumab and methotrexate, however; not all listed therapies were necessarily administered during the same time periods or in the sequence they appear.

²IT trastuzumab was titrated within the listed dose range based on patient tolerability.

³Patient was still receiving intrathecal trastuzumab plus thiotepa at the time of the report.

Laufman LR, Forsthoefel KF. Use of intrathecal trastuzumab in a patient with carcinomatous meningitis. Clin Breast Cancer 2001;2:235 (letter).

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Stemmler HJ, Mengele K, Schmitt M, Harbeck N, Laessig D, Hermann KA, . Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: A case report. Anticancer Drugs 2008;19:832–6.

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Ferrario C, Davidson A, Bouganim N, Aloyz R, Panasci LC. Intrathecal trastuzumab and thiotepa for leptomeningeal spread of breast cancer. Ann Oncol 2009;20:792–5 (letter).

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