Cancer Treatment

Stem cell transplantation for anaplastic lymphoma

Diffuse large-cell lymphoma is the most common form of NHL, and autologous stem cell transplantation has been shown to be beneficial in some subsets with this illness. For patients with diffuse large-cell lymphoma who relapse from a CR but remain chemotherapy-responsive, autologous transplantation is the treatment of choice. At the present time, high-risk patients who achieve a CR after a full course of standard-dose chemotherapy and have a high risk for relapse may derive the most benefit from stem cell transplantation.

For anaplastic lymphoma specifically, a phase II trial that used high-dose chemotherapy and autologous stem cell transplantation (ASCT) as front-line treatment revealed a 5-year overall survival rate of 87%, which was significantly better than for aggressive nonanaplastic lymphomas. To date, no published randomized trials compare ASCT to conventional combination chemotherapy regimens. NCCN has no recommendations for anaplastic or ALK negative lymphoma. ALK negaive lymphomas have a poorer prognosis than ALK positive ones.

 

H. Bertz, R. Zeiser, W. Lange, S. Fetscher, C. F. Waller, and J. Finke
Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index
Ann. Onc., September 1, 2004; 15(9): 1419 - 1424.

M. D. Caballero, J. A. Perez-Simon, A. Iriondo, J. J. Lahuerta, J. Sierra, J. Marin, M. Gandarillas, R. Arranz, J. Zuazu, V. Rubio, A. Fernandez de Sevilla, E. Carreras, J. Garcia-Conde, J. Garcia-Larana, C. Grande, A. Sureda, M. J. Vidal, J. Rifon, C. Perez-Equiza, R. Varela, J. M. Moraleda, J. C. Garcia Ruiz, C. Albo, R. Cabrera, J. F. San Miguel, and E. Conde
High-dose therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group
Ann. Onc., January 1, 2003; 14(1): 140 - 151.

Deconinck E, Lamy T, Foussard C, et al. Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial. Br J Haematol. Jun 2000;109(4):736-42.

S G Holtan, A L Feldman, R A Knudson, R P Ketterling and L F Porrata
Failure of front-line autologous transplant in anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma Bone Marrow Transplantation , (6 September 2010)

Venous stenting for venous obstruction

Venous stents are being increasingly used as an effective tool during percutaneous endovenous intervention (PEVI). The major indication for PEVI has been venous stenosis and external compression, which often leads to deep venous thrombosis (DVT). This is a technique that is only recently coming into wider use but there is significant literature support for its effectiveness. Visualization of patency is required for this procedure and MRI/MRV would supply such an evaluation..

1. Sharifi M, Mehdipour M, Berkovits A, et al. Low restenosis rate of stents placed in peripheral venous circulation. Catheter Cardiovasc Interv 2010;75:S83–S84.
2. Neglén P, Darcey R, Olivier J, Raju S. Bilateral stenting at the iliocaval confluence. J Vasc Surg 2010;51:1457–1466.
3. Neglén P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: Long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007;46:979–990.
4. Neglén P, Raju S. In-stent recurrent stenosis in stents placed in the lower extremity venous outflow tract. J Vasc Surg 2004;39:181–187.

Rituxan for CD20 positive myeloma

Interest in using Rituxan for subsets of myeloma with CD20 positivity, was provoked by a Phase II study of Moreau et al evaluating four weekly infusions of single-agent rituximab (375 mg/m2) therapy in a cohort of patients with CD20+ multiple myeloma (MM) with either stage I, never treated disease, or stage III MM in relapse, or refractory after two lines of therapy. The authors concluded that rituximab as a single agent had minor activity in this cohort of patients with CD20 expression on at least 33% of tumor cells. A 2008 review concluded: "Clinical trials show that anti-CD20 therapy with rituximab elicits a partial response in approximately 10% of CD20+ patients with multiple myeloma. In addition, there is preliminary evidence of disease stabilization in 50-57% of CD20+ patients for a period of 10-27 months. Further large-scale clinical trials are therefore needed to establish the role of this promising strategy in the treatment of myeloma." There are several other reports in different settings, including in maintenance.

All in all, there is sufficient literature to consider it supported.

J M Bergua, C Cabrera, E G Arteta and J Prieto
Rituximab in CD20 positive multiple myeloma, Letter to the Editor, Leukemia 22, 1082-1083 (May 2008)

P Moreau, L Voillat, L Benboukher, C Mathiot, C Dumontet, N Robillard, O Hérault, F Garnache, R Garand, N Varoqueaux, H Avet-Loiseau, J L Harousseau and R Bataille
Rituximab in CD20 positive multiple myeloma, Leukemia 21, 835-836 (April 2007)

Kapoor P, Greipp PT, Morice WG, Rajkumar SV, Witzig TE, Greipp PR.
Anti-CD20 monoclonal antibody therapy in multiple myeloma.
Br J Haematol. 2008 Apr;141(2):135-48. Epub 2008 Mar 3.

Long-term response to maintenance treatment with rituximab in CD20+ multiple myeloma
Hitoshi OhnoLeukemia & Lymphoma
November 2010, Vol. 51, No. 11 : Pages 2144-2146

 

Triptorelin in prostate cancer

Triptorelin is a gonadotropin-releasing hormone agonist. By causing constant stimulation of the pituitary, it decreases pituitary secretion of gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). Like other GnRH agonists, triptorelin may be used in the treatment of hormone-responsive cancers such as prostate cancer. TRELSTAR DEPOT is indicated in the palliative treatment of advanced prostate cancer. It offers an alternative treatment for prostate cancer when orchiectomy or estrogen administration are either not indicated or unacceptable to the patient.

 

Watson Pharma. Trelstar LA 11.25 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA: 2006 Aug.

Heyns, Chris F Triptorelin in the Treatment of Prostate Cancer: Clinical Efficacy and Tolerability, American Journal of Cancer:
2005 - Volume 4 - Issue 3 - pp 169-183

 

 

Xeliri is supported by current medical literature for first or second line treatment of metastatic colon cancer. There are several phase II studies that indicate effectiveness. For example, a 2009 study enrolled 53 patients: 29 (55%) were 65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR + stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhea occurred in 8 (15%) patients and grade 1–2 hand–foot syndrome in 7 (13%) patients. It concluded that  Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients.

Whereas Xelox and irinotecan is listed by NCCN (REC-E, 2011), Xeliri is not.

 Anna Pessino, Alberto Sobrero Optimal treatment of metastatic colorectal cancer Expert Review of Anticancer Therapy 2006 6:5, 801-812

Dan S. Zuckerman, Jeffrey W. Clark Systemic therapy for metastatic colorectal cancer Cancer
112(9), 1879-1891

CP Garcia-Alfonso et al, apecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI groupBritish Journal of Cancer (2009) 101, 1039–1043

Capecitabine (X) plus irinotecan (XELIRI) as first-line treatment for metastatic colorectal cancer (MCRC): Final safety findings from a phase II trial.Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 3602 

Hepatocellular carcinoma and Folfox

A randomized study of Folfox was presented in the 2010 ASCO meeting. When compared with doxorubicin after 266 events, the FOLFOX4 regimen significantly improved median progression-free survival from 1.77 to 2.93 months (P = .0002) in the EACH trial. Overall survival also improved from 4.97 to 6.40 months, although the difference failed to reach statistical significance at that point (P = .0695),  At taht meeting, Dr. Qin presented updated efficacy results after 305 events that left survival rates virtually unchanged, but pushed overall survival to statistical significance (4.90 vs. 6.47 months), but pushed overall survival to statistical significance at a P value of .0425).
Response rates (complete and partial responses) by RECIST (Response Evaluation Criteria in Solid Tumors) were 8.7% for FOLFOX4 and 2.7% for doxorubicin (P = .0142). Disease control rates (complete and partial responses and stable disease) were 53% for FOLFOX4 vs. 32% for doxorubicin (P less than .0001).

While these are preliminary results and not truly peer-reviewed, they represent the first survival advantage reproted for HCC for any chemo regimen.

V. Boige et al, Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial Br J Cancer 97, 862-867, 207

Votrient for thyroid cancer

Votrient is a multi-targeted tyrosine kinase inhibitor and it is currently approved for renal cell carcinoma. A recent study evaluated it in thyroid cancer. This phase II strial included 37 patients who had received up to two prior therapies, had measurable disease, and whose disease had progressed in the six months before they were enrolled in the study. Patients received 800 mg of Votrient daily.

• Following a median of 12 four-week cycles of treatment with Votrient, there were 18 partial responses (PRs) to therapy.
• Researchers estimated that PRs would last for one year in 66% of patients.
• Median progression-free survival was 11.7 months.
• Overall survival at one year was 81%.
• When PR was measured according to thyroid cancer cell type, eight PRs were observed in11 patients with follicular cell type (72.7%), five PRs in 11 patients with Hürthle cell type (45.4%), and five PRs in 15 patients with papillary cell type (33.3%).
• 66.7% of patients who were antithyroidglobulin-negative (no antibodies to the protein thyroidglobulin, produced by the thyroid) experienced a decrease in thyroidglobulin of more than 30%.
• Side effects were modest, but 15 patients did require a dose reduction due to adverse effects. Frequent side effects included diarrhea and hypertension.

The researchers concluded that Votrient is highly active in advanced differentiated thyroid cancer and well tolerated; the drug may therefore be a promising treatment for patients with this disease. Votrient will be further evaluated in this patient population in an upcoming Phase III clinical trial.

NCCN (p.FOLL-5) mentions Votrient as a level 2B recommendations in a footnote when clinical trials are not avaialble for this specific uncommon situation.

Bible KC, Suman VJ, Molina JR, et at. Evidence of clinical efficacy of the multi-targeted tyrosine kinase inhibitor pazopanib in rapidly progressive radioiodine-refractory metastatic differentiated thyroid cancers: results of the Phase 2 consortium study MC057H. Presented at the 14^th International Thyroid Congress, Paris, France, September 11-16, 2010. Abstract OC-022.

MammaPrint

Mammaprint is a test that idenitifies a profile of a tumor sample that is then used to assess risk. In February 2005, the BlueCross BlueShield Association Technology Evaluation Center (TEC) conducted a technology assessment on gene expression profiling for managing breast cancer treatment.  The TEC Assessment summarized the evidence for four different gene expression profiling assays, in various stages of development, that are intended for eventual use in identifying those patients at low risk of recurrence for whom adjuvant chemotherapy can be avoided. The four assays were the 21-gene Oncotype DX (Genomic Health), the 70-gene MammaPrint® (Agendia; also referred to as the “Amsterdam signature”), the 76-gene “Rotterdam signature” (Veridex), and a 41-gene signature reported by Ahr and colleagues. Because current selection methods by traditional clinical and histopathological criteria exclude only a small proportion from adjuvant chemotherapy, and only a small proportion derive significant benefit, it is likely that a significant number of women could avoid the side effects of chemotherapy if more accurate selection methods were available. However, the TEC Assessment concluded that because published evidence supporting clinical utility is not available, the evidence for all of the gene expression panels is insufficient to permit conclusions concerning the effect of gene expression profiling on selecting patients who do not need chemotherapy for the purpose of avoiding adverse outcomes, while maintaining or improving disease-free or overall survival outcomes.by Paik and colleagues discussed above. 

Sicne then, NCCN has recommended Oncotype but not Mammaprint. The two tests are not identical and Oncotype recommendation by NCCN does not translate into an approval for Mammaprint, as per Californai Tachn Assessment Forum(http://www.gopathdx.com/?action-model-name-research-itemid-13) and Medicare(http://palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~Jurisdiction%201%20Part%20B~Articles~General~7WLQ5C4784?open&navmenu=Articles%7C%7C%7C%7C).

de Snoo, F. A., Knauer, M., Bender, R. A., Stork-Sloots, L., Rutgers, E. J., Glas, A. M., Linn, S. C., Van 't Veer, L. J.
Outcome prediction by the 70-gene profile in the context of the National Comprehensive Cancer Network (NCCN) guidelines
J Clin Oncol (Meeting Abstracts) 2009 27: 535

http://www.springerlink.com/content/03vw93w25440442u/fulltext.pdf

2007 TEC Assessment: Gene expression profiling for managing breast cancer treatment. www.bcbs.com/tec/vol20/20_03.html

National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Breast Cancer. http://nccn.org/professionals/physician_gls/PDF/breast.pdf

 

Juvenile Myelomonocytic Leukemia

Smith FO, Loh ML. Myelodysplastic and myeloproliferative syndrome in children. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Silberstein LE, McGlave P, et al., editors. Hematology: basic principles and practice. 5th ed. Philadelphia (PA): Churchill Livingstone; 2008.

Juvenile myelomonocytic leukemia is a type of a myelodysplastic syndrome. The only treatment that has resulted in cures for JMML is a bone marrow transplant, with about a 50% survival rate. The risk of relapsing after transplant is high, and has been recorded as high as 50%. However, there is no other treatment that has a comparative cure rate and allogeneic transpalntation is supported by a number of studies as well as revieews and is recommended by PDQ.

 Taussig DC, Davies AJ, Cavenagh JD, Oakervee H, Syndercombe-Court D, Kelsey S, et al. Durable remissions of myelodysplastic syndrome and acute myeloid leukemia after reduced-intensity allografting. J Clin Oncol. 2003 Aug 15;21(16):3060-5.

Yoshimi A, Mohamed M, Bierings M, Urban C, Korthorf E, Zecca M, et al. Second allogeneic hematopoietic stem cell transplantation (HSCT) results in outcome similar to that of first HSCT for patients with juvenile myelomonocytic leukemia. Leukemia. 2007 Mar;21(3):556-60. Epub 2007 Feb 1.

Yusuf U, Frangoul HA, Gooley TA, Wooolfrey AE, Carpenter PA, Andrews RG, et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marroe Transplant. 2004Apr;33(8)805-14.