Cancer Treatment Today » Sarcoma

Doxil for soft tissue sarcoma – pro

M Levin, MD — Wed, 09 Jan 2013 20:32:34 +0000

Doxorubicin has been used for soft tissue sarcoma(STS) since the first report in 1972, and more recently, its pegylated form has also been studied. A study by Judson et al, found that it had has equivalent activity to doxorubicin in STS with an improved toxicity profile. In this randomized phase II trial, Doxil (50 mg/m2 every four weeks) was compared to unencapsulated doxorubicin (75 mg/m2 every three weeks). Although Doxil was well tolerated and appeared to have similar efficacy compared to doxorubicin, the response rates in both arms were low, 10 and 9 percent, respectively. This is not a very encouraging response rate. Grenadier et al, however, raised an issue of response rates possibly not correlating with long term survival. NCCN does list Doxil under single drug options for STS.

Alexander I. Spira and David S. Ettinger, The Use of Chemotherapy in Soft-Tissue Sarcomas he Oncologist August 2002 vol. 7 no. 4 348-359

Judson I, Radford JA, Harris M et al. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2001;37:870877.

Chidiac T, Budd GT, Pelley R et al. Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas. Invest New Drugs 2000;18:253259.

Grenader T, Goldberg A, Hadas-Halperin I, Gabizon A. Long-term response to pegylated liposomal doxorubicin in patients with metastatic soft tissue sarcomas. Anticancer Drugs 2009; 20:15.

nccn.org, Soft TIssue Sarcoma, SARC-E, 1.

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Sinitinib for Extraskeletal Myxoid Chondrosarcoma – pro

M Levin, MD — Fri, 21 Dec 2012 15:54:24 +0000

Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct and rare sarcoma that tends to be indolent but to eventually recurr locally and metastastzise. The 2009 review by Drilon highlighted ineffectiveness of chemotherapy and emphasized an agressive approach to local control. There are , however, two case reports showing excellent responses to chemotherapy. Radiotherapy is sometimes helpful. Sutent was effective in two cases reported by Stacchiotti et al. On the other hand, the one patient with EMC in a study of multiple non-GIST sarcomas had no response to sunitinib(George et al). The problem with basing therapy decisions on case reports is that there is a bias to publish only the positive cases; in this context, the single negative case is highly significant. Clearly more study is warranted before suntinib is used routinely for this admittedly rare cancer.

REFERENCES:
Drilon AD, Popat S, Bhuchar G, D’Adamo DR, Keohan ML, Fisher C, Antonescu CR, Singer S, Brennan MF, Judson I, Maki RG. Extraskeletal myxoid chondrosarcoma: a retrospective review from 2 referral centers emphasizing long-term outcomes with surgery and chemotherapy. Cancer. 2008 Dec 15;113(12):3364-71.

Kun Han, Yuan-Jue Sun, Zan Shen, Jian-jun Zhang, Feng Lin, Hui Zhao, Saleem Meerani, Yang Yao
Extraskeletal myxoid chondrosarcoma: a case report of complete remission by chemotherapy and review of the literature. BMJ Case Reports 2010; doi:10.1136/bcr.07.2009.2128

Suzanne George, Priscilla Merriam, Robert G. Maki, Annick D. Van den Abbeele, Jeffrey T. Yap, Timothy Akhurst, David C. Harmon, Gauri Bhuchar, Margaret M. O’Mara, David R. D’Adamo, Jeffrey Morgan, Gary K. Schwartz, Andrew J. Wagner, James E. Butrynski, George D. Demetri, and Mary L. Keohan, Multicenter Phase II Trial of Sunitinib in the Treatment of Nongastrointestinal Stromal Tumor Sarcomas, JCO VOLUME 27 NUMBER 19 JULY 1 2009

K, Fujiwara T, Beppu Y, Chuman H, Yoshida A, Kawano H, Kawai A; Extraskeletal myxoid chondrosarcoma: a review of 23 patients treated at a single referral center with long-term follow-up; Ogura Archives of Orthopaedic and Trauma Surgery (Jun 2012), http://www.docguide.com/extraskeletal-myxoid-chondrosarcoma-review-23-patients-treated-single-referral-center-long-term-foll?tsid=5

Stacchiotti S, Dagrada GP, Morosi C, Negri T, Romanini A, Pilotti S, Gronchi A, Casali PG.
Extraskeletal myxoid chondrosarcoma: tumor response to sunitinib.Clin Sarcoma Res. 2012 Oct 11;2(1):22.

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Sorafenib for desmoid tumors – pro

M Levin, MD — Mon, 17 Dec 2012 16:29:33 +0000

Desmoid tumors, also called aggressive fibromatosis, deep musculoaponeurotic fibromatosis, and fibrosarcoma grade I of the desmoid type, do not generally metastasize but can cause pain and compromise organs. Few treatments for this condition are well established, although many novel agents are being studied. Among them is Nexavar (sorafenib). The basis for the interest in this drug is that it appears to inhibit MPNST cell growth in vitro.

A recent study of sorafenib in children with neurofabromatosis was not able to establish the minmally tolerated dose. A series from Sloan Kettering used sorafenib as first-line therapy in 11/26 patients and the remaining 15/26 had received a median of 2 prior lines of therapy. Twenty-three of 26 patients had shown evidence of progressive disease by imaging, whereas 3 patients had achieved maximum benefit or toxicity with chemotherapy. Sixteen of 22 (∼70%) patients reported significant improvement of symptoms. At a median of 6 months (2-29) of treatment, the best response evaluation criteria in solid tumors (RECIST) 1.1 response included 6/24 (25%) patients with partial response (PR), 17/24 (70%) with stable disease, and 1 with progression and death. NCCN lists sorafenib on p. SARC-E and references the Goundar paper as the basis for its recommendation.

See also here for a more general discussion of chemotherapy for desmoid tumors.

Other options, see here and here and here

For Lay version see here

CLINICAL SUMMARY:
39 year-old woman who had been treated with Doxil and experimental therapies of fibromatosis adn nwo Nexvar is being proposed.

REFERENCES:
23.Ambrosini G, Cheema HS, Seelman S, et al. Sorafenib inhibits growth and mitogen-activated protein kinase signaling in malignant peripheral nerve sheath cells. Mol Cancer Ther. Apr 2008;7(4):890-6.

Kim A, Dombi E, Tepas K, Fox E, Martin S, Wolters P, Balis FM,Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas.Pediatr Blood Cancer. 2012 Sep 7.

Current Perspectives on Desmoid Tumors: The Mayo Clinic ApproachCancers 2011, 3, 3143-3155

Gounder MM, Lefkowitz RA, Keohan ML, et al. Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 2011; 17:4082.

nccn, Soft TIssue Sarcoma, 2012

Votrient for GIST – pro

M Levin, MD — Thu, 29 Nov 2012 15:48:21 +0000

Pazopanib(Votrient) is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and KIT. These are important pathways for GIST tumors and several trials looked into using pazopanib for GIST. Although initial studies suggested that the drug is not effective for GIST, more recently a phase II study of 25 patients and a randomized study of 86 patients suggest that it is.The results of PAZOGIST, a randomised phase II study of pazopanib plus best supportive care (BSC) vs BSC alone in patients with unresectable metastatic and/or locally-advanced gastrointestinal stromal tumours (GIST), who are resistant or experienced toxicity to previous treatments with standard doses of imatinib and sunitinib, show an improvement in progression-free survival (PFS) in favour of pazopanib arm. The study was presented by Prof. Jean-Yves Blay of the University Claude Bernard Lyon I, Centre Léon Bérard, Lyon, France during the Proffered Paper session in Sarcoma at ESMO Congress 2014 in Madrid, Spain. The primary endpoint was PFS. It was planned to include 80 patients to detect an improvement in the 4-month PFS rate from 15% in the BSC arm alone to 45% in the pazopanib plus BSC with 5% two-sided α error and 80% power. Secondary objectives included overall survival (OS), objective response rate at 4 months, best response rate and tolerance.

P. G. Casali & J.-Y. Blay,Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upAnnals of Oncology 21 (Supplement 5): v98–v102, 2010

nccn, GIST 2012

Nishida T, Hirota S, Yanagisawa A, Sugino Y, Minami M, Yamamura Y, Otani Y, Shimada Y, Takahashi F, Kubota T; GIST Guideline Subcommittee.
Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version.Int J Clin Oncol. 2008 Oct;13(5):416-30.

K. N. Ganjoo et al, A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib. Ann Oncol (2014) 25 (1): 236-240.

ESMO Abstract LBA45 – A randomized multicentre phase II study of pazopanib plus best supportive care (BSC) vs BSC alone in metastatic gastroIntestinal stromal tumors (GIST) resistant to imatinib and sunitinib, 2014.

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SCT for SVI – pro

M Levin, MD — Thu, 13 Sep 2012 18:31:57 +0000

Severe combined immunodeficiency (SCID) is a serious, life-threatening condition with high morbidity and mortality. SCID, a group of rare genetic disorders characterized by profound abnormalities in the development and function of the T and B lymphocytes and natural killer cells, was first reported more than 50 years ago. In the past two decades, great advances have been made in the understanding and treatment of SCID. A variety of molecular defects have recently been found to cause SCID, including defects in the gene encoding the common gamma chain (X-linked form), adenosine deaminase deficiency (ADA), interleukin-7 receptor deficiency, janus tyrosine kinase-3 (JAK-3) deficiency and recombinase activating gene (RAG)-1 and RAG-2 deficiency.1,2 The two most common forms of SCID are the X-linked SCID (about 50% of all cases) and those due to an ADA deficiency (about 15-20%). Because the disease is rare, no prospective studies of treatment are possible and it is usually classified in studies with a larger group of inherited immunoeficienceis or genetic syndromes. There are no phase II stuides; only case series and reports.
The first ever successful transplant for SCID was performed in 1968. Over the past several decades, the outcome for SCID as a whole has improved dramatically, and a number of large retrospective registry studies have documented the success in improving overall survival (OS) and immunologic recovery. The improvements are due to a number of different factors, including earlier diagnosis, better pre- and post-HSCT supportive care, improved HLA typing, the availability of compatible donors from unrelated volunteer and cord blood banks, and less toxic chemotherapy regimens to prepare patients for HSCT. Many of the major studies have tended to look at SCID as a whole, and outcomes have been presented for all types of SCID. However, the rapid advances in gene identification technology now allow us to make specific diagnoses.

Hyper IgM syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling and recurrent infections. Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.The way to look at this disease as it being in a spectrum of immunodeficiency disease, for which replacement of the bone marrow from another individual removes immunodeficiency and cures it.

Diaz de Heredia C, Ortega JJ, Diaz MA, Olive T, Badell I, Gonzalez-Vicent M, et al. Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies. Bone Marrow Transplant. 2008 Apr;41(7):627-33.

Allewelt H et al, Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience.Pediatr Blood Cancer. 2015 Dec;62(12):2216-22.

Immunodeficiency Foundation Diagnostic and Clincial Care Guidelines for Primary Immunodeficiency Disease, IDF 2008 chrome-extension://oemmndcbldboiebfnladdacbdfmadadm/http://primaryimmune.org/wp-content/uploads/2011/04/IDF-Diagnostic-Clinical-Care-Guidelines-for-Primary-Immunodeficiency-Diseases-2nd-Edition.pdf

Griffith LM, Cowan MJ, Kohn DB, et al. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol 2008; 122:1087.

Inborn Errors Working Party (IEWP)
UPDATED! EBMT/ESID GUIDELINES FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PI
Home/ Working Parties/ Inborn Errors Working Party (IEWP)/ Resources/ UPDATED! EBMT/ESID GUIDELINES FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PI
Published: Dec 01, 2011

There is sufficient evidence in various reports over these two decades to consider it medically necessary.

Beser OF1, Conde CD, Serwas NK, Cokugras FC, Kutlu T, Boztug K, Erkan T.Clinical features of interleukin 10 receptor gene mutations in children with very early-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):332-8.

H. Bobby Gaspar, Waseem Qasim, E. Graham Davies, Kanchan Rao, Persis J. Amrolia, Paul Veys, How I treat severe combined immunodeficiency.
Blood 2013 122:3749-3758

Elhasid R, Rowe JM. Hematopoietic stem cell transplantation in neutrophil disorders: severe congenital neutropenia, leukocyte adhesion deficiency and chronic granulomatous disease. Clin Rev Allergy Immunol. 2010 Feb;38(1):61-7.

Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, et al. Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood. 2009 Apr 23;113(17):4114-24.

Steward and Jarisch Haemopoietic stem cell transplantation for genetic disorders
Arch Dis Child.2005; 90: 1259-1263

Fischer A. Severe combined immunodeficiencies (SCID). Clin Exp Immunol 2000; 122: 143-9.

Buckley RH. Advances in the understanding and treatment of human severe combined immunodeficiency. Immunol Res 2000; 22(2-3): 237-51.

Docetaxel/ gemcitabine for sarcoma – pro

M Levin, MD — Thu, 13 Sep 2012 18:29:26 +0000

Docetaxel and gemcitabine is a well described regimen in soft tissue sarcoma. Hensley examined gemcitabine and docetaxel in a phase II study of patients with metastatic leiomyosarcoma. That study also examined the pharmacokinetics of gemcitabine in a 30- and 90-minute infusion schedule on separate cycles of therapy, described above. The study enrolled 34 patients, all but five with uterine leiomyosarcoma, and demonstrated a surprising response rate of 53% (three complete responses, 15 PRs). Importantly, 50% of patients previously treated with doxorubicin responded. The median time to progression was 5.6 months, and the median survival duration was 17.9 months. This study was impressive in its demonstration of uterine leiomyosarcoma as a subtype relatively sensitive to this chemotherapy combination, and also indicated that part of the reason for this high response rate was the synergy of gemcitabine and docetaxel, given the 21% response rate for gemcitabine alone in second-line therapy in a Gynecologic Oncology Group (GOG) study and low response rate of docetaxel against sarcomas in first- and second-line therapy in phase II and randomized phase II studies.
These data were supported by two other clinical studies of patients consecutively treated with gemcitabine and docetaxel at the University of Michigan and in a retrospective analysis of patients treated with gemcitabine plus docetaxel in France. In the clinical analysis from Michigan, the response rate for patients treated mostly with first- and second-line therapy was 43%; the response rate in the French cohort of patients receiving any number of lines of prior therapy was 18%. These data confirmed the activity of gemcitabine and docetaxel in leiomyosarcoma, with patients with a few other histologies responding as well.

The question remained whether the activity of gemcitabine and docetaxel lay in the fixed-dose-rate infusion schedule (10 mg/m2 per minute) or in the synergy between gemcitabine and docetaxel. The Sarcoma Alliance for Research through Collaboration (SARC) performed a randomized phase II study to examine this question, comparing between patients given a higher dose fixed-dose-rate infusion of gemcitabine and those given a lower dose of fixed-dose-rate gemcitabine and docetaxel. A novel Bayesian clinical trial design was employed that randomized patients to the better therapy as the study proceeded. The details of the model and the interpretation of the study design are described elsewhere. In all, 73 patients were randomized to the two-drug combination, and 49 were randomized to gemcitabine as a single agent, indicating in and of itself the superiority of the combination. The response rate for gemcitabine was 9%, versus 16% for gemcitabine and docetaxel, and more patients on the combination took longer to progress than on the single agent, accounting for the model’s imbalance of randomization in favor of the combination.

NCCN lists this regimen as recommended for soft tissue sarcoma. However, a number of questions about schedule, sequence and kinetics remain and there are still trials ongoing to answer them.

R. G. Maki, M. L. Hensley, J. K. Wathen, S. R. Patel, D. A. Priebat, S. Okuno, D. Reinke, P. F. Thall, R. S. Benjamin, L. H. Baker,A SARC multicenter phase III study of gemcitabine (G) vs. gemcitabine and docetaxel (G+D) in patients (pts) with metastatic soft tissue sarcomas (STS). Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 9514

Bay JO, Ray-Coquard I, Fayette J, Leyvraz S, Cherix S, Piperno-Neumann S, Chevreau C, Isambert N, Brain E, Emile G, Le Cesne A, Cioffi A, Kwiatkowski F, Coindre JM, Bui NB, Peyrade F, Penel N, Blay JY;Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.Int J Cancer. 2007 Jan 15;120(2):450.

Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future
Robert G. Maki The Oncologist, Vol. 12, No. 8, 999-1006, August 2007; doi:10.1634/theoncologist.12-8-999

http://nccn.org/professionals/physician_gls/PDF/sarcoma.pdf

Topotecan and cytoxan for relapsed Ewing’s sarcoma – pro

M Levin, MD — Thu, 13 Sep 2012 18:23:51 +0000

Ewing sarcoma geenrally responds to chemotherapy. The prognosis in relapse is poor. Promising response rates have been reported for the combination of topotecan (TOPO) and cyclophosphamide (CYC). IN such cases, one can usually obtain a response and prolongation of life but not a cure. ESMO guidelines recommend palliative treatment in relapse and this would include well-based regimens such as topotecan and cytoxan.

Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H.
Pediatr Blood Cancer. 2006 Nov;47(6):795-800.Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors.

Saylors RL 3rd, Stine KC, Sullivan J, Kepner JL, Wall DA, Bernstein ML, Harris MB, Hayashi R, Vietti TJ; Pediatric Oncology Group.Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study.J Clin Oncol. 2001 Aug 1;19(15):3463-9.

http://annonc.oxfordjournals.org/cgi/reprint/18/suppl_2/ii79

Saeter G, Ewing’s sarcoma of bone: ESMO clinical recommendations for diagnosis, treatment and follow-up.ESMO Guidelines Working Group, .Ann Oncol. 2007 Apr;18 Suppl 2:ii79-80.

Irinotecan for rhabdomyosarcoma – pro

M Levin, MD — Thu, 13 Sep 2012 18:22:13 +0000

Rhabdomyosarcoma arising from skeletal muscle is the most common soft tissue sarcoma of childhood. Approximately 20% of patients present with disseminated disease and have a poor prognosis with combined modality therapy. The remaining 80% of patients present with localized disease and cure rates with combined modality therapy range from 50% to 90% depending on histology, site of disease and the ability of surgery to completely remove all gross and microscopic disease. Patients with recurrent rhabdomyosarcoma have a very poor prognosis and are usually treated with chemotherapy. Active agents for the treatment of recurrent or refractory rhabdomyosarcoma include Cytoxan® (cyclophosphamide), Ifex® (ifosfamide), Adriamycin® (doxorubicin), Actinomycin D® (dactinomycin), Vepesid® (etoposide), Platinol® (cisplatin) and Paraplatin® (carboplatin). A previous study showed a complete or partial response to Camptosar and Cytoxan in 10 of 15 patients with recurrent rhabdomyosarcoma.

Researchers affiliated with the U.S. Children’s Oncology Group reported the outcome of two consecutive trials. In the first trial, patients were initially treated with Camptosar alone. Patients who experienced a partial or complete disappearance of cancer after two cycles of Camptosar then received additional treatment with Camptosar and Oncovin® (vincristine) alternating with the commonly used VAC chemotherapy regimen (Oncovin, Actinomycin D and Cytoxan. Patients who did not respond to treatment with Camptosar received additional treatment with VAC alone. The first trial was closed early due to a high rate of progressive disease (32%) among children who were initially treated with Camptosar alone. The researchers noted, “The unexpectedly high rate of progression seen with Camptosar alone precludes us from recommending the use of this single agent for the treatment of rhabdomyosarcoma.”

The second trial had a similar design, but evaluated the combination of Camptosar and Oncovin, rather than Camptosar alone. Patients who responded to Camptosar and Oncovin received additional treatment with these two drugs alternating with VAC. Patients who did not respond to Camptosar and Oncovin received additional treatment with VAC alone. In the combination trial, 70% of children experienced a partial or complete disappearance of detectable cancer, and only 8% experienced progressive disease. In spite of the promising response rate, survival among children initially treated with Camptosar and Oncovin was similar to that among children treated with VAC alone.

Gastrointestinal problems (abdominal pain, diarrhea, and dehydration) were the most common side effects among children treated with Camptosar and Oncovin. These researchers concluded that the combination of Camptosar and Oncovin is highly active against metastatic rhabdomyosarcoma, and that this combination warrants further testing in intermediate-risk patients with rhabdomyosarcoma.

In the second report researchers affiliated with the French Society of Pediatric Oncology and the United Kingdom Children’s Cancer Study Group reported that Camptosar alone resulted in an overall response rate of 11.4% with one complete response in 35 heavily pretreated patients with rhabdomyosarcoma.The time to disease progression was 1.4 months and the median survival was 5.8 months.

Dacarbazine (DTIC) and temozolomide are similar imidazotetrazine alkylators that methylate DNA at nucleophilic sites. Dacarbazine requires hepatic P450 biotransformation to monomethyl triazenoimidazole carboxamide (MTIC). Temozolomide is orally bioavailable, more lipophilic, and spontaneously converted to MTIC, and it also seems to generate less nausea. Except for phase I studies in patients with solid tumors that included rhabdomyosarcoma, there are no prospective trials for irinotecan and Tmodar, to my knowledge in rhabdomyosarcoma, although there is some evidence of activity in neuroblastoma and Ewings. There are ongoing trials with this combination and cetuximab.

Comments: These data suggest that Camptosar could be a useful agent for the treatment of rhabdomyosarcoma. However, its utility in far advanced patients is not remarkable as a single agent. Adding Camptosar to other drugs earlier in the disease course would be of interest.

Pappo AS, Lyden E, Breitfeld P et al. Two consecutive Phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the children’s oncology group. Journal of Clinical Oncology 2007;25:362-369.

Vassal G, Couanet D, Stockdale E, et al. Phase III trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: A joint study of the French Society of Pediatric Oncology and the United Kingdom Children’s Cancer Study Group. Journal of Clinical Oncology 2007:356-361.

Wagner, et al. Temozolomide and intavenous irinotecan for treatment of advanced Ewing Sarcoma. Pediatr Blood Cancer 2007; 48:132-139.

UpToDate, Rhabdomyosarcoma and undifferentiated sarcoma in childhood and adolescence: Treatment

Casey, et al. Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan-Kettering experience. Pediatr Blood Cancer 2009; 53:1029-1034.

See: http://professional.cancerconsultants.com/oncology_sarcoma_cancer_news.aspx?id=39107

Adjuvant chemotherapy for oseosarcoma – pro

M Levin, MD — Thu, 13 Sep 2012 18:20:38 +0000

Despite an optimal loco-regional treatment, 35%–50% of patients with sarcoma will develop metastasis. Systemic chemotherapy is then the standard treatment; the active drugs are doxorubicin and ifosfamide and, to a lesser extent, dacarbazine. In the adjuvant setting, NCCN recommends “a combination of two of the following agents: doxorubicin, ifosfamide, high dose methotrexate and growth factors”(p.10).

If there had been neoadjuvant chemo, as in this case, adjuvant therapy appears to be ineffective. A second course of chemotherapy for osteosarcoma after a neoadjuvant course and surgical resection does not appear to increase survival, but does increase the risk of a secondary malignancy and complications resulting from neutropenia. Still NCCN recommends chemo even after neo-adjuvant chemotherapy. On p.21 NCCN recommends continuing the same chemo, not a different chemo, adjuvantly. The Europena Guideline says: ”
Although most protocols include both pre- and postoperative chemotherapy, this has not been proven to add survival benefit over postoperative chemotherapy alone”. I consider a different chemo regimen than the preop regimen to be investigational.

BEREND Keith R et al, Adjuvant chemotherapy for Osteosarcoma may not increase survival after neoadjuvant chemotherapy and surgical resection Journal of surgical oncology 2001, vol. 78, no3, pp. 162-170 (31 ref.)

G. Saeter ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of osteosarcoma Ann Oncol 14: 1165-1166. 2005

nccn.org, bone cancer 2012

Histiocytic sarcoma – pro

M Levin, MD — Thu, 13 Sep 2012 18:19:14 +0000

Histiocytic sarcoma (HS) is a rare neoplasm of uncertain etiology. Most recently, the diagnostic criteria for this entity have been revised with inclusion of diagnostic modalities such as immunohistochemical and cytogentic techniques. HS tends to have an aggressive clinical course and presents with systemic symptoms of fever, weight loss, adenopathy, hepatosplenomegly, rash, and pancytopenia. There is no standard treatment and no comparative studies to the rarity of this disease. Thalidomide is a promising agent that may exert a therapeutic benefit but thus far it is supported only by case reports. A 2006 Health Technology Assessment (HTA): Usefulness of thalidomide for the management of sarcomas concluded that evidence supporting it in other sarcomas and even in Kaposi’s, where it has been studied the most, is anecdotal.

Muneer H. Abidi et al Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant American Journal of Hematology Volume 82 Issue 10, Pages 932 – 933

http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=32006000897