Recurrent Multicentric Glioblastoma Multiforme = Responds to Thalidomide and Chemotherapy

From: Subject: Recurrent Multicentric Glioblastoma Multiforme Responds to Thalidomide and Chemotherapy Date: Fri, 8 Feb 2008 23:17:16 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C86AA8.BEBD34E0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C86AA8.BEBD34E0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.cancernetwork.com/print.jhtml;jsessionid=BVMU2DTHAKP24QSNDLRSKHSCJUNN2JVN?articleID=178601387&url_prefix= Recurrent Multicentric Glioblastoma Multiforme = Responds to Thalidomide and Chemotherapy


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Recurrent=20 Multicentric Glioblastoma Multiforme Responds to Thalidomide and=20 Chemotherapy

URL: http://www.cancernetwo= rk.com/showArticle.jhtml;jsessionid=3DBVMU2DTHAKP24QSNDLRSKHSCJUNN2JVN?ar= ticleId=3D178601387=20

Glioblastoma multiforme remains virtually = incurable, with reported median survivals of less than 2 years = with=20 standard treatment.[1] In recent years, thalidomide (Thalomid) has = shown=20 activity in high-grade gliomas as a single agent and in = combination=20 with nitrosoureas and carboplatin (Paraplatin).[2-4] I will = describe three=20 cases in which patients with recurrent, multicentric glioblastoma=20 responded to thalidomide plus chemotherapy after failing initial = treatment=20 with conventional radiation and chemotherapy for a single = malignant=20 glioma.

Case 1

A 43-year-old man diagnosed with anaplastic astrocytoma = underwent a=20 right frontal craniotomy and gross total resection in July 1998. = The=20 surgery was followed by external-beam radiation therapy and four = cycles of=20 cisplatin, etoposide, and vincristine. In December 1999, disease=20 progression was found, and treatment was switched to single-agent=20 temozolomide (Temodar). Disease continued to progress, and = multiple=20 enhancing lesions were documented in February 2000 (Figure 1).

The patient then received six cycles of procarbazine = (Matulane),=20 lomustine (CCNU [CeeNu]), and vincristine in combination with = daily=20 thalidomide at a dose of 400 mg. Initial dose escalation of = thalidomide to=20 600 mg/d was not well tolerated, and thereafter, the dose was = maintained=20 at 400 mg/d. Complete resolution of all lesions was observed after = four=20 cycles of therapy (see Figure 2, p 278).

Mild thrombocytopenia and leukopenia resolved upon completion = of=20 therapy with procarbazine, lomustine, and vincristine. Minor = sensory=20 peripheral neuropathy was noted but did not prevent the patient = from=20 working full time while receiving treatment. At 1=BD years after = disease=20 recurrence, the patient continues to receive single-agent = thalidomide.

Cases 2 and 3

Two other cases involving combination chemotherapy and = thalidomide=20 after failure of first-line therapy resulted in partial responses = at our=20 institution. In both cases, the patients were women with a history = of=20 breast cancer. Single brain lesions were initially suspected to be = metastatic disease, but surgical resection identified them as = primary=20 anaplastic astrocytoma. These neoplasms did not respond to = treatment with=20 radiation therapy and temozolomide, and the disease progressed to = multiple=20 enhancing lesions in each patient, with a brain biopsy-confirmed = diagnosis=20 of glioblastoma multiforme.

Both patients subsequently received the combination of = cisplatin,=20 etoposide, and vincristine plus thalidomide (200 mg/d) and = achieved=20 partial responses (> 50% tumor reduction) after two = cycles, with=20 durable responses of 16 and 24 weeks. Escalation of the = thalidomide dose=20 to 400 mg/d was possible in one patient; the other was maintained = at 200=20 mg/d after experiencing somnolence at higher doses. One patient = died as a=20 result of chemotherapy-induced thrombocytopenia, and the other = died due to=20 complications of meningeal carcinomatosis.

Conclusions

These cases suggest that the addition of thalidomide to = standard=20 chemotherapy regimens containing a nitrosourea, procarbazine, = cisplatin,=20 or etoposide may considerably enhance activity in patients with = recurrent=20 multicentric high-grade and malignant glioma. The implications of = this=20 preliminary experience in patients with a poor prognosis and few = viable=20 treatment options suggest that further study of thalidomide in = combination=20 with chemotherapy is warranted in this setting.

Surasak Phuphanich, MD
Associate Professor, Chief, = Neurology=20 Service, Director, Division of Neurooncology, H. Lee Moffitt = Cancer Center=20 & Research Institute, Tampa, Florida

References

1. Louis DN, Cavenee WK: Neoplasms of the central nervous = system, in:=20 DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles = &=20 Practice of Oncology, 6th ed, pp 2091-2160. Philadelphia, = Lippincott=20 Williams & Wilkins, 2001.

2. Fine HA, Figg WD, Jaeckle K, et al: Phase II trial of = the=20 antiangiogenic agent thalidomide in patients with recurrent = high-grade=20 gliomas. J Clin Oncol 18:708-715, 2000.

3. Fine HA, Maher EA, Wen PY, et al: Phase II trial of = thalidomide=20 and BCNU in recurrent high-grade gliomas (abstract 218). Proc Am = Soc Clin=20 Oncol 20:55a, 2001.

4. Glass J, Gruber ML, Nirenberg A: Phase I/II study of=20 carboplatin and thalidomide in recurrent glioblastoma multiforme = (abstract=20 551). Proc Am Soc Clin Oncol 18:144a, 1999.

=20

Copyright = =A9 2007 CMP=20 Healthcare Media Group LLC, a United Business Media company
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BORDER-TOP: 1px dotted; = PADDING-LEFT: 5px; PADDING-BOTTOM: 5px; MARGIN: 0px auto; BORDER-LEFT: = 1px dotted; WIDTH: 800px; PADDING-TOP: 5px; BORDER-BOTTOM: 1px dotted; = BACKGROUND-COLOR: #fff } #site_header { PADDING-RIGHT: 10px; PADDING-LEFT: 10px; FONT-SIZE: small; = PADDING-BOTTOM: 10px; VERTICAL-ALIGN: middle; COLOR: white; PADDING-TOP: = 10px; HEIGHT: 60px; BACKGROUND-COLOR: #020187 } #site_header_promo_links { FLOAT: right; FONT: 10px/110% Verdana, Arial, Helvetica, sans-serif; = WIDTH: 380px; COLOR: #fff; MARGIN-RIGHT: 10px; TEXT-ALIGN: right } #site_header_promo_links LI { PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 0px; = PADDING-TOP: 3px; LIST-STYLE-TYPE: none } #site_header_promo_links A { COLOR: #ffffff } #container2 { CLEAR: both; WIDTH: 800px; BACKGROUND-COLOR: #fff } #container935 { CLEAR: both; WIDTH: 935px; BACKGROUND-COLOR: #fff } #maincontent { =09 } .blocklabel_boxed { PADDING-RIGHT: 2px; PADDING-LEFT: 5px; FONT-WEIGHT: bold; FONT-SIZE: = 10px; 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} A.header-yellow:hover { FONT-WEIGHT: normal; FONT-SIZE: 12px; COLOR: #ffff99; FONT-FAMILY: = Arial, Helvetica, sans-serif; TEXT-DECORATION: underline } .white1 { FONT-WEIGHT: normal; FONT-SIZE: 12px; COLOR: #ffffff; FONT-FAMILY: = Arial, Helvetica, sans-serif; TEXT-DECORATION: none } .white-bold { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #ffffff; FONT-FAMILY: Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } .blue-bold { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #99ccff; FONT-FAMILY: Arial, = Helvetica, sans-serif; TEXT-DECORATION: none } #top_ad_container { BORDER-RIGHT: 0px; PADDING-RIGHT: 0px; BORDER-TOP: gray 1px solid; = PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; BORDER-LEFT: 0px; PADDING-TOP: = 0px; BORDER-BOTTOM: gray 1px solid } ------=_NextPart_000_0000_01C86AA8.BEBD34E0--