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Lani · 08-23-2009, 01:09 PM

new pubmed search part 1:J Neurooncol. 2009 Jun 26. [Epub ahead of print] Links

Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy.

Clatot F, Philippin-Lauridant G, Ouvrier MJ, Nakry T, Laberge-Le-Couteulx S, Guillemet C, Veyret C, Blot E.
Département d'Oncologie Médicale, Centre Henri-Becquerel, Rue d'Amiens, 76038, Rouen Cedex, France.
Leptomeningeal meningitis occurs in approximately 5% of metastatic breast cancers, and there is no standard treatment for this complication. We retrospectively analyzed the clinical data and cerebrospinal fluid of 24 patients treated with high-dose intrathecal methotrexate for breast cancer leptomeningeal meningitis (BLM). Cytologic response (CSF cytology without neoplastic cells after treatment) was observed in 11 patients (46%) and related to survival (P = 0.005). In addition, clinical symptoms improved in all 11 patients who had a cytologic response and in 7 patients (54%) without cytologic response (P = 0.02). The predictive value of cytologic response needs further confirmation. Cytologic response could be helpful in the management of intrathecal chemotherapy in patients with BLM.
PMID: 19557501 [PubMed - as supplied by publisher]
^^^^
Neurol Sci. 2009 Jun;30(3):251-4. Epub 2009 Mar 4. Links

Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report.

Gaviani P, Silvani A, Corsini E, Erbetta A, Salmaggi A.
Neuro Oncology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. paola.gaviani@istituto-besta.it
Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte).
PMID: 19259616 [PubMed - in process]

Related
&&&
Cancer. 2009 May 1;115(9):1947-53.Links

Intracranial dural metastases.

Nayak L, Abrey LE, Iwamoto FM.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
BACKGROUND:: Intracranial dural metastases (IDM) are found at autopsy in 9% of patients with advanced systemic cancer. However, to the authors' knowledge, IDM have not been studied systematically in the modern neuroimaging era. The objective of the current study was to evaluate the demographics, clinical presentation, imaging, treatment, and prognosis of patients with IDM. METHODS:: The current study was a retrospective review of 122 patients with IDM diagnosed at Memorial Sloan-Kettering Cancer Center between 1999 and 2006. Patients with concurrent brain or leptomeningeal metastases were excluded. RESULTS:: Sixty-one percent of the patients were women; the median age at diagnosis was 59 years, the median Karnofsky performance scale (KPS) at diagnosis was 80, and the median time to IDM diagnosis from initial cancer diagnosis was 37 months. Breast (34%) and prostate (17%) cancers were the most frequent primary tumors associated with IDM. Fifty-six percent of patients had a single dural metastasis. On imaging, 70% had metastases of the overlying skull, 44% had dural tail metastases, 53% had vasogenic edema, and 34% had brain invasion. Direct extension from skull metastases was the most common mode of spread. Eighty-three percent of patients had active systemic disease at the time of IDM diagnosis. A lower KPS and lung cancer were associated with worse overall survival. Surgical resection and chemotherapy improved progression-free survival, but only resection was found to be associated with improved overall survival. CONCLUSIONS:: IDM affect a significant proportion of cancer patients. KPS and status of systemic cancer should guide treatment decisions. Cancer 2009. (c) 2009 American Cancer Society.
PMID: 19241421 [PubMed - indexed for MEDLINE]
^^^^

Annals of Oncology 2009 20(4):

letters to the editor

Intrathecal trastuzumab and thiotepa for leptomeningeal spread of breast cancer

A 31-year-old woman underwent a right segmental mastectomy in October 1999 for a pT2, pN2 invasive ductal carcinoma, negative for estrogen receptor/progesterone receptor, positive for amplification of human epidermal growth factor receptor-2 (HER-2). She received adjuvant chemotherapy (doxorubicin + cyclophosphamide, followed by paclitaxel) and local radiotherapy. Two and a half years after surgery, she developed multiple liver metastases. She received i.v. carboplatin, paclitaxel, and trastuzumab, followed by capecitabine and trastuzumab, with a radiological completeresponse. Approximately 14 months later (April 2004), a single brain lesion was detected on magnetic resonance imaging (MRI), in the right occipital lobe. The lesion was surgically resected, followed by external beam whole-brain radiation. In August 2006, the patient presented with visual impairment, ptosis of the right eye, right hemi-facial hypoesthesia, left foot drop, andparalysis of the left facial nerve. An MRI exam revealed a right occipital brain lesion (1.5 cm), diffuse leptomeningeal metastases (LM), a cervical extramedullary intradural enhancing lesion (C1–C3), an intramedullary lesion centered at T12, and a nodular area of enhancement on the roots of the cauda equina. Only a suspicious 6-mm lung nodule was found on systemic restaging. A diagnostic lumbar puncture was carried out, and cytology of the cerebro-spinal fluid (CSF) was positive for cancer cells (5% of malignant cells). CSF glucose, lactate dehydrogenase, and protein levels were always normal.
After placement of an Ommaya reservoir, she was started on intrathecal (i.t.) trastuzumab, initially on a weekly schedule, with gradual dose increase from 20 to 30 mg (Table 1), later combined with i.t. methotrexate (10 mg) for two doses. To reduce the risk of anaphylaxis and neurotoxicity from the preservative agent [1], i.t. trastuzumab was administered without the diluent provided. Interestingly, after the first dose of i.t. trastuzumab, all subsequent CSF cytologies were negative for malignant cells. After the two first doses of i.t. trastuzumab, we also started i.v. trastuzumab, that was never interrupted afterwards, and i.v. pegylated liposomal doxorubicin (PLD; Caelyx/Doxil®) (see Table 1 for details of i.t. and i.v. treatments). She also received radiotherapy to the lower thoracic–lumbar spine. After the second dose of i.v. PLD, she developed prolonged grade 2 fatigue, grade 3 anemia, grade 3 neutropenia, and grade 2 lethargy. Nevertheless, there was an improvement in visual acuity and ambulation plus resolution of her headaches and eye ptosis. A repeat brain MRI showed a decrease in size and enhancement of the supra- and infratentorial lesions and no new lesions. After she recuperated from toxicity, the i.t. trastuzumab wasrestarted at the dose of 40 mg every 3 weeks and was maintained for 8 months, during which her symptoms slowly improved, even with concomitant steroid withdrawal. Furthermore, new MRI/positron emission tomography studies confirmed a remarkable response in both the spinal cord lesion and the brain LM. In July 2007, 10 months after i.t. trastuzumab was started, a new MRI showed an enlargement of the lesions in the supra- and infratentorial levels, even in the absence of new central nervous system (CNS) lesions or new symptoms. I.t. trastuzumab (40 mg) was continued every 3 weeks, adding i.t. thiotepa 10 mg. The treatment was overall well tolerated, except for one episode of right face Herpes zoster which rapidly resolved. After 6 months of continuous i.t. treatment at such doses, the i.t. trastuzumab was increased to 50 mg and the i.t. thiotepa to 12 mg every 3 weeks, and these doses were administered from February 2008 until August 2008. The treatment was remarkably well tolerated, even when combined with i.v. chemotherapy (vinorelbine, paclitaxel), in the presence of systemic progression (lungs, sternum, breast). Restaging of the CNS lesions in January 2008, after five cycles with combined thiotepa, revealed that all the lesions were stable or slightly decreased. However, another MRI of the brain in May 2008, as compared with January 2008, demonstrated a significant improvement, with some LM significantly decreasing in size, and other lesions no longer visualized (Figure 1). The patient remains well and is fully functional at this time. She has only residual facial paralysis.

View this table:
[in this window]
[in a new window]

Table 1. Time line of intrathecal and i.v. treatments (September 2006–August 2008)

View larger version (99K):
[in this window]
[in a new window]
[Download PowerPoint slide]
Figure 1. Improvement of MRI findings after increase in the doses of intrathecal trastuzumab and thiotepa.

HER-2-positive cancers have a higher rate of dissemination to CNS [2]. An aggressive treatment on the CNS involvement was particularly justified in our patient, given that the disease was systemically well controlled. Nevertheless, symptomatic dissemination to the leptomeninges usually carries a short-term prognosis [3], and i.t. treatment in most cases has a minor impact [4]. Five reports of i.t. trastuzumab were published so far [5–9]. I.t. thiotepa [5] or methotrexate [8] was also given in two cases. Our report offers further evidence on the safety of i.t. trastuzumab and strongly suggests that this approach can have a significant impact on HER-2-positive LM: our patient is alive and with an excellent performance status (Eastern Cooperative Oncology Group 0) after >2 years since the diagnosis of heavily symptomatic LM. During this time, she has been almost continuously treated with i.t. trastuzumab, efficiently delivered using an Ommaya reservoir. Initially, it was particularly difficult to evaluate the effectiveness of the treatment, as symptoms took several months to clearly improve, even if CSF cytology became negative after the first i.t. injection. The positive results of the first MRI led us to continue the i.t. treatment, even in the presence of an ambiguous clinical evolution. This suggests that MRI imaging could be the best single parameter to evaluate treatment efficacy and to predict a clinical benefit.
Our experience suggests that it is safe to combine i.t. trastuzumab with systemic trastuzumab-based chemotherapy regimens. Our patient had more side-effects with concomitant liposomal doxorubicin, given shortly after radiotherapy to the spine and when her performance status was still poor, while concomitant weekly schedules ofvinorelbine or paclitaxel with i.v. trastuzumab were both characterized by a remarkable lack of toxicity. It is not possible to distinguish between the effect of i.t. and i.v. treatments on our patient's CNS metastases, but most likely the i.t. treatment had a major role in achieving long-term control of meningeal disease. Trastuzumab is unable to cross the blood–brain barrier [10], and even after neurosurgery and radiotherapy, the i.t. concentration of trastuzumab is significantly lower than the serum concentration. Significantly higher levels can be achieved through i.t. administration [6].

The combination of i.t. trastuzumab with thiotepa is particularly promising. We suggest that 50 mg of i.t. trastuzumab and 12 mg of i.t. thiotepa can be safely administered in repeated 3-week cycles. A number of preclinical studies showed a significant synergism between these two agents [11]. Indeed, after progression on single-agent i.t. trastuzumab, the LM in our patients were controlled with the addition of thiotepa, and the most relevant radiological response was reported after an increase of the i.t. doses of both drugs. No steroid was given at this time and thus this is not a confounding factor in the response to the treatment.

Even if meningeal carcinomatosis is not accurately ‘measurable’, as per RECIST criteria, this is one of few reports of a radiological response of meningeal metastases to a medical treatment, associated with the longest survival reported with i.t. trastuzumab after diagnosis of LM.

C. Ferrario*, A. Davidson, N. Bouganim, R. Aloyz and L. C. Panasci

Department of Oncology, McGill University, Lady Davis Institute at Jewish General Hospital, Montréal, Québec, Canada

* (E-mail: cristianoferrario@gmail.com)

^^^^^

Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report.
Anticancer Drugs. 2008 Sep; 19(8):832-6.
[Anticancer Drugs. 2008]
High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer.
Ann Oncol. 2008 Nov; 19(11):1978-80. Epub 2008 Oct 9.
[Ann Oncol. 2008]
Intrathecal chemotherapy in carcinomatous meningitis from breast cancer.
Anticancer Res. 2002 Sep-Oct; 22(5):3057-9.
[Anticancer Res. 2002]
ReviewLeptomeningeal metastasis.
Cancer Invest. 2005; 23(2):145-54.
[Cancer Invest. 2005]
ReviewManagement of leptomeningeal malignancy.
Expert Opin Pharmacother. 2005 Jun; 6(7):1115-25.
[Expert Opin Pharmacother. 2005]

08-23-2009, 01:09 PM	#11
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	Re: Update: Spinal Fluid me new pubmed search part 1:J Neurooncol. 2009 Jun 26. [Epub ahead of print] Links Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy. Clatot F, Philippin-Lauridant G, Ouvrier MJ, Nakry T, Laberge-Le-Couteulx S, Guillemet C, Veyret C, Blot E. Département d'Oncologie Médicale, Centre Henri-Becquerel, Rue d'Amiens, 76038, Rouen Cedex, France. Leptomeningeal meningitis occurs in approximately 5% of metastatic breast cancers, and there is no standard treatment for this complication. We retrospectively analyzed the clinical data and cerebrospinal fluid of 24 patients treated with high-dose intrathecal methotrexate for breast cancer leptomeningeal meningitis (BLM). Cytologic response (CSF cytology without neoplastic cells after treatment) was observed in 11 patients (46%) and related to survival (P = 0.005). In addition, clinical symptoms improved in all 11 patients who had a cytologic response and in 7 patients (54%) without cytologic response (P = 0.02). The predictive value of cytologic response needs further confirmation. Cytologic response could be helpful in the management of intrathecal chemotherapy in patients with BLM. PMID: 19557501 [PubMed - as supplied by publisher] ^^^^ Neurol Sci. 2009 Jun;30(3):251-4. Epub 2009 Mar 4. Links Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report. Gaviani P, Silvani A, Corsini E, Erbetta A, Salmaggi A. Neuro Oncology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. paola.gaviani@istituto-besta.it Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte). PMID: 19259616 [PubMed - in process] Related &&& Cancer. 2009 May 1;115(9):1947-53.Links Intracranial dural metastases. Nayak L, Abrey LE, Iwamoto FM. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. BACKGROUND:: Intracranial dural metastases (IDM) are found at autopsy in 9% of patients with advanced systemic cancer. However, to the authors' knowledge, IDM have not been studied systematically in the modern neuroimaging era. The objective of the current study was to evaluate the demographics, clinical presentation, imaging, treatment, and prognosis of patients with IDM. METHODS:: The current study was a retrospective review of 122 patients with IDM diagnosed at Memorial Sloan-Kettering Cancer Center between 1999 and 2006. Patients with concurrent brain or leptomeningeal metastases were excluded. RESULTS:: Sixty-one percent of the patients were women; the median age at diagnosis was 59 years, the median Karnofsky performance scale (KPS) at diagnosis was 80, and the median time to IDM diagnosis from initial cancer diagnosis was 37 months. Breast (34%) and prostate (17%) cancers were the most frequent primary tumors associated with IDM. Fifty-six percent of patients had a single dural metastasis. On imaging, 70% had metastases of the overlying skull, 44% had dural tail metastases, 53% had vasogenic edema, and 34% had brain invasion. Direct extension from skull metastases was the most common mode of spread. Eighty-three percent of patients had active systemic disease at the time of IDM diagnosis. A lower KPS and lung cancer were associated with worse overall survival. Surgical resection and chemotherapy improved progression-free survival, but only resection was found to be associated with improved overall survival. CONCLUSIONS:: IDM affect a significant proportion of cancer patients. KPS and status of systemic cancer should guide treatment decisions. Cancer 2009. (c) 2009 American Cancer Society. PMID: 19241421 [PubMed - indexed for MEDLINE] ^^^^ Annals of Oncology 2009 20(4): letters to the editor Intrathecal trastuzumab and thiotepa for leptomeningeal spread of breast cancer A 31-year-old woman underwent a right segmental mastectomy in October 1999 for a pT2, pN2 invasive ductal carcinoma, negative for estrogen receptor/progesterone receptor, positive for amplification of human epidermal growth factor receptor-2 (HER-2). She received adjuvant chemotherapy (doxorubicin + cyclophosphamide, followed by paclitaxel) and local radiotherapy. Two and a half years after surgery, she developed multiple liver metastases. She received i.v. carboplatin, paclitaxel, and trastuzumab, followed by capecitabine and trastuzumab, with a radiological completeresponse. Approximately 14 months later (April 2004), a single brain lesion was detected on magnetic resonance imaging (MRI), in the right occipital lobe. The lesion was surgically resected, followed by external beam whole-brain radiation. In August 2006, the patient presented with visual impairment, ptosis of the right eye, right hemi-facial hypoesthesia, left foot drop, andparalysis of the left facial nerve. An MRI exam revealed a right occipital brain lesion (1.5 cm), diffuse leptomeningeal metastases (LM), a cervical extramedullary intradural enhancing lesion (C1–C3), an intramedullary lesion centered at T12, and a nodular area of enhancement on the roots of the cauda equina. Only a suspicious 6-mm lung nodule was found on systemic restaging. A diagnostic lumbar puncture was carried out, and cytology of the cerebro-spinal fluid (CSF) was positive for cancer cells (5% of malignant cells). CSF glucose, lactate dehydrogenase, and protein levels were always normal. After placement of an Ommaya reservoir, she was started on intrathecal (i.t.) trastuzumab, initially on a weekly schedule, with gradual dose increase from 20 to 30 mg (Table 1), later combined with i.t. methotrexate (10 mg) for two doses. To reduce the risk of anaphylaxis and neurotoxicity from the preservative agent [1], i.t. trastuzumab was administered without the diluent provided. Interestingly, after the first dose of i.t. trastuzumab, all subsequent CSF cytologies were negative for malignant cells. After the two first doses of i.t. trastuzumab, we also started i.v. trastuzumab, that was never interrupted afterwards, and i.v. pegylated liposomal doxorubicin (PLD; Caelyx/Doxil®) (see Table 1 for details of i.t. and i.v. treatments). She also received radiotherapy to the lower thoracic–lumbar spine. After the second dose of i.v. PLD, she developed prolonged grade 2 fatigue, grade 3 anemia, grade 3 neutropenia, and grade 2 lethargy. Nevertheless, there was an improvement in visual acuity and ambulation plus resolution of her headaches and eye ptosis. A repeat brain MRI showed a decrease in size and enhancement of the supra- and infratentorial lesions and no new lesions. After she recuperated from toxicity, the i.t. trastuzumab wasrestarted at the dose of 40 mg every 3 weeks and was maintained for 8 months, during which her symptoms slowly improved, even with concomitant steroid withdrawal. Furthermore, new MRI/positron emission tomography studies confirmed a remarkable response in both the spinal cord lesion and the brain LM. In July 2007, 10 months after i.t. trastuzumab was started, a new MRI showed an enlargement of the lesions in the supra- and infratentorial levels, even in the absence of new central nervous system (CNS) lesions or new symptoms. I.t. trastuzumab (40 mg) was continued every 3 weeks, adding i.t. thiotepa 10 mg. The treatment was overall well tolerated, except for one episode of right face Herpes zoster which rapidly resolved. After 6 months of continuous i.t. treatment at such doses, the i.t. trastuzumab was increased to 50 mg and the i.t. thiotepa to 12 mg every 3 weeks, and these doses were administered from February 2008 until August 2008. The treatment was remarkably well tolerated, even when combined with i.v. chemotherapy (vinorelbine, paclitaxel), in the presence of systemic progression (lungs, sternum, breast). Restaging of the CNS lesions in January 2008, after five cycles with combined thiotepa, revealed that all the lesions were stable or slightly decreased. However, another MRI of the brain in May 2008, as compared with January 2008, demonstrated a significant improvement, with some LM significantly decreasing in size, and other lesions no longer visualized (Figure 1). The patient remains well and is fully functional at this time. She has only residual facial paralysis. View this table: [in this window] [in a new window] Table 1. Time line of intrathecal and i.v. treatments (September 2006–August 2008) View larger version (99K): [in this window] [in a new window] [Download PowerPoint slide] Figure 1. Improvement of MRI findings after increase in the doses of intrathecal trastuzumab and thiotepa. HER-2-positive cancers have a higher rate of dissemination to CNS [2]. An aggressive treatment on the CNS involvement was particularly justified in our patient, given that the disease was systemically well controlled. Nevertheless, symptomatic dissemination to the leptomeninges usually carries a short-term prognosis [3], and i.t. treatment in most cases has a minor impact [4]. Five reports of i.t. trastuzumab were published so far [5–9]. I.t. thiotepa [5] or methotrexate [8] was also given in two cases. Our report offers further evidence on the safety of i.t. trastuzumab and strongly suggests that this approach can have a significant impact on HER-2-positive LM: our patient is alive and with an excellent performance status (Eastern Cooperative Oncology Group 0) after >2 years since the diagnosis of heavily symptomatic LM. During this time, she has been almost continuously treated with i.t. trastuzumab, efficiently delivered using an Ommaya reservoir. Initially, it was particularly difficult to evaluate the effectiveness of the treatment, as symptoms took several months to clearly improve, even if CSF cytology became negative after the first i.t. injection. The positive results of the first MRI led us to continue the i.t. treatment, even in the presence of an ambiguous clinical evolution. This suggests that MRI imaging could be the best single parameter to evaluate treatment efficacy and to predict a clinical benefit. Our experience suggests that it is safe to combine i.t. trastuzumab with systemic trastuzumab-based chemotherapy regimens. Our patient had more side-effects with concomitant liposomal doxorubicin, given shortly after radiotherapy to the spine and when her performance status was still poor, while concomitant weekly schedules ofvinorelbine or paclitaxel with i.v. trastuzumab were both characterized by a remarkable lack of toxicity. It is not possible to distinguish between the effect of i.t. and i.v. treatments on our patient's CNS metastases, but most likely the i.t. treatment had a major role in achieving long-term control of meningeal disease. Trastuzumab is unable to cross the blood–brain barrier [10], and even after neurosurgery and radiotherapy, the i.t. concentration of trastuzumab is significantly lower than the serum concentration. Significantly higher levels can be achieved through i.t. administration [6]. The combination of i.t. trastuzumab with thiotepa is particularly promising. We suggest that 50 mg of i.t. trastuzumab and 12 mg of i.t. thiotepa can be safely administered in repeated 3-week cycles. A number of preclinical studies showed a significant synergism between these two agents [11]. Indeed, after progression on single-agent i.t. trastuzumab, the LM in our patients were controlled with the addition of thiotepa, and the most relevant radiological response was reported after an increase of the i.t. doses of both drugs. No steroid was given at this time and thus this is not a confounding factor in the response to the treatment. Even if meningeal carcinomatosis is not accurately ‘measurable’, as per RECIST criteria, this is one of few reports of a radiological response of meningeal metastases to a medical treatment, associated with the longest survival reported with i.t. trastuzumab after diagnosis of LM. C. Ferrario, A. Davidson, N. Bouganim, R. Aloyz and L. C. Panasci Department of Oncology, McGill University, Lady Davis Institute at Jewish General Hospital, Montréal, Québec, Canada (E-mail: cristianoferrario@gmail.com) ^^^^^ Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs. 2008 Sep; 19(8):832-6. [Anticancer Drugs. 2008] High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol. 2008 Nov; 19(11):1978-80. Epub 2008 Oct 9. [Ann Oncol. 2008] Intrathecal chemotherapy in carcinomatous meningitis from breast cancer. Anticancer Res. 2002 Sep-Oct; 22(5):3057-9. [Anticancer Res. 2002] ReviewLeptomeningeal metastasis. Cancer Invest. 2005; 23(2):145-54. [Cancer Invest. 2005] ReviewManagement of leptomeningeal malignancy. Expert Opin Pharmacother. 2005 Jun; 6(7):1115-25. [Expert Opin Pharmacother. 2005]