Cancer Treatment

IVIG in CLL

The hypogammaglobinemia and impaired T-cell function associated with chronic lymphocytic leukemia (CLL) predispose patients to potentially serious infections. Patients who demonstrate a pattern of repeated infections, such as pneumonia and septicemia, should be treated monthly with prophylactic parenteral gamma globulin. In the initial study published in 1988, the survival probability of patients with initial levels of gammaglobulin of less than 700 mg/dl was significantly lower (P = 0.03) than in patients with initial levels of 700 mg/dl or more. NCCN recommends IVIG prophylaxis when there are recurrent infections requiring antibiotics or hospitalization and IGG levels are below 500. IVIG is FDA indicated for CLL. For Chronic lymphocytic leukemia teh recommended dose is  0.3-0.6 mg/kg every 3-4 weeks.

Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. Jun 15 2008;111(12):5446-56. [Medline].

Abbott BL. Chronic lymphocytic leukemia: recent advances in diagnosis and treatment. Oncologist. Jan 2006;11(1):21-30

NCCN.ORG, CLL, p.15

PET and CAT for followup of Hodgkin's

How to follow Hodgkin's after a documented remission is controversial. Historically,  follow-up protocols were based on a report generated in 1999 by pathologists, radiologists and oncologists from the Cotswolds meeting in 1999. This report recommended that patients be assessed every 3 months during the first 2 years post-therapy, every 4 months during the third year, every 6 months during the fourth and fifth years, and annually thereafter. However, subsequent literature has continued to question the need for such frequent imaging. The uncertainty about the value of routine radiological investigations in the detection of relapse has increased after two studies showed that most relapses are detected as a result of patient-reported symptoms, not radiological investigations. Farther uncertainty was introduced by availability of PET scans. American College of Radiology recommends CT scans every 6 months for two years, then annually for 3 years but lists PET as "no consensus". BC guidelines dont recommend any CT scanning. NCCN recommends CT scans of chest and abdomen every 6 months for two years and says that "Surveillance PET should not be done routinely...management decisions should not be made on PET scan alone...".That is also ESMO recommendation of 2010.

 

 

Ng AK, Constine LS, Deming RL, Wolkov HB, Hoppe RT, Abrams RA, Mendenhall NP, Morris DE, Yahalom J, Chauvenet A, Hudson MM, Winter JN, Mauch PM, Expert Panel on Radiation Oncology-Hodgkin's Disease Work Group. Follow-up of Hodgkin's Disease. [online publication]. Reston (VA): American College of Radiology (ACR); 2005. 6 p. [43 references]

E T Dryver et al, Follow-up of patients with Hodgkin's disease following curative treatment: the routine CT scan is of little value British Journal of Cancer (2003) 89, 482–486.

ESMO - http://annonc.oxfordjournals.org/content/21/suppl_5/v168.full

http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Lymphoma/HodgkinsDisease.htm

Maeda LS, Horning SJ, Iagaru AH, et al. Role of FDG-PET/CT surveillance for patients with classical Hodgkin’s disease in first complete response: the Stanford University experience [abstract]. Blood 2009;114:Abstract 1563.

Zinzani PL, Stefoni V, Tani M, et al. Role of [18F]fluorodeoxyglucose positron emission tomography scan in the follow-up of lymphoma. J Clin Oncol 2009;27:1781–1787.

nccn.org, Hodgkin, 2011

Chemotherapy for sinonasal carcinoma

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive neoplasm of the paranasal sinuses, which has recently been characterized as a distinct pathologic entity. The prognosis for patients with SNUC is poor. There is only case report level information on the usefullness of chemotherapy for this condition and most of these indicate that it is not very effective. Etoposide is supported by a few reports, mostly in combination but without significant reported effectiveness. It can only be considered experimental based on the lack of information and suggestions of it not being effective.

Mamoru Miyaguchia1  Lymph node and distant metastases in patients with sinonasal carcinoma
The Journal of Laryngology & Otology (1995), 109:304-307

 Eric R. Schmidt, Ronald L. Berry Diagnosis and Treatment of Sinonasal Undifferentiated Carcinoma: Report of a Case and Review of the Literature
Journal of Oral and Maxillofacial Surgery, Volume 66, Issue 7, July 2008, Pages 1505-1510

Transplantation Proceedings, Volume 40, Issue 10, December 2008, Pages 3821-3822
P. De Simone, L. Coletti, D. Campani, A. Falcone, F. Filipponi  Liver Transplantation for Metastatic Sinonasal Undifferentiated Carcinoma: A Case Report

Brian S. Kim  et al,  Sinonasal Malignancies of Neuroendocrine Origin
Hematology/Oncology Clinics of North America, Volume 22, Issue 6, December 2008, Pages 1297-1316

Rituxan for Gullain-Barre syndrome

Guillain-Barré syndrome is a disorder in which the body's immune system attacks part of the peripheral nervous system. Symptoms include varying degrees of weakness or tingling sensations in the legs. Sometimes, the weakness and abnormal sensations spread to the arms and upper body and progress to paralysis. There is no known cure for Guillain-Barré syndrome, but therapies can lessen the severity of the illness and accelerate the recovery in most patients. Currently, plasmapheresis and high-dose immunoglobulin therapy are most often used.

GB syndrome can occurr is association with various conditions, as a paraneopastic syndrome or secondary to a viral infection. Rituximab has also been reported to be associated with causing GB, probably through its anti-immune effect. There are also reports of rituximab association with improvement in GB. Review of the literature finds only case report level evidence to support rituximab for GB. The plan states: "Experimental means any treatment where the stated proposed treatment has no supporting literature for safety or efficacy in human trials". Since this is the case for rituximab for GB, it should be considered investigational.

Ostronoff F, Perales MA, Stubblefield MD, Hsu KC.Rituximab-responsive Guillain-Barré syndrome following allogeneic hematopoietic SCT.Bone Marrow Transplant. 2008 Jul;42(1):71-2.

Carmona, Alberto1; Alonso, Juan; Heras, Manuel; Navarrete, AgustínGuillain-Barre syndrome in a patient with diffuse large B-cell lymphoma, and rituximab maintenance therapy. An association beyound anecdotal evidence?  Clinical and Translational Oncology, Volume 8, Number 10, October 2006 , pp. 764-766(3)

Terenghi F, Ardolino G, Nobile-Orazio EGuillain-Barré syndrome after combined CHOP and rituximab therapy in non-Hodgkin lymphoma.Peripher Nerv Syst. 2007 Jun;12(2):142-3.

CIalis for erectile dysfuncton after prostate cancer

Erectile dysfunction is common among patients treated for prostate cancer. It is greatest among those treated with prostatectomy;  More than half of men who undergo radical prostatectomy for prostate cancer experience erectile dysfunction. It also occurrs among those treated iwth radiation and seed implants. More than 80% of prostate cancer patients develop erectile dysfunction (ED) as a result of treatment, regardless of whether they have surgery or external beam radiation therapy. Less clear is how it can be surmounted. One study shoed that Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer. Another study is ongoing:
Sildenafil in Treating Erectile Dysfunction in Patients With Prostate Cancer, NCT00057759. Cialis appears to imprve erectile dysfunctoni in two randomized European trials. I consider it supported by medical llterature.

David C. Miller, John T. Wei, Rodney L. Dunn, James E. Montie, Hector Pimentel, Howard M. Sandler, P. William McLaughlin and Martin G. Sanda. Use of medications or devices for erectile dysfunction among long-term prostate cancer treatment survivors: Potential influence of sexual motivation and/or indifference Urology, Volume 68, Issue 1 , July 2006, Pages 166-171

RISK OF ERECTILE DYSFUNCTION SIMILAR FOR DIFFERENT PROSTATE CANCER TREATMENTS
CA Cancer J Clin 2001 51: 148-149
 
Incrocci L, Slob AK, Hop WC. Tadalafil (Cialis) and erectile dysfunction after radiotherapy for prostate cancer: an open-label extension of a blinded trial.Urology. 2007 Dec;70(6):1190-3.

Eardley I, Gentile V, Austoni E, Hackett G, Lembo D, Wang C, Beardsworth A.
Efficacy and safety of tadalafil in a Western European population of men with erectile dysfunction.BJU Int. 2004 Oct;94(6):871-7.

JX-594

JX-594, is engineered based on the vaccinia virus strain and is genetically modified by deleting its thymidine kinase gene to enhance cancer-selectivity. In addition, it has been joined to with GM-CSF gene to stimulate systemic anti-tumoral immune response in the context of product replication and lysis of the infected cancer cells. In a recent pashe I trial, presented at the American Society of Gene Therapy (ASGT) Annual Meeting in
Boston, Massachusetts in June 2008, JX-594 demonstrated that the product was well-tolerated and resulted in clear anti-cancer efficacy in patients with liver cancer. Three patients with advanced treatment-refractory hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) were treated with JX-594. Objective radiographic responses were demonstrated. Serum tumor markers, which correlate with tumor burden over time in patients, decreased by up to 95 percent after treatment. JX-594 replication, its release into the circulation and distant tumor targeting and infection were demonstrated.

Another study that was presented reported 14 patients with a variety of treatment-refractory cancer types (e.g. liver, colon, lung) in the liver were treated every three weeks with JX-594 by ultrasound-guided intratumoral injection. Patients had advanced cancers that had failed all available therapies and were therefore considered terminal. Responses were reproted.

This is clearly a promising therapy but more research is needed before it can be widely adopted.

J. H. Kim etal, Systemic Armed Oncolytic and Immunologic Therapy for Cancer with JX-594, a Targeted Poxvirus Expressing GM-CSF Molecular Therapy (2006) 14, 361–370

B. Park, T. Hwang, T. Liu, D. Sze, J. Kim, H. Kwon, S. Oh, S. Han, J. Yoon, S. Hong
Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial The Lancet Oncology, Volume 9, Issue 6, Pages 533-542

 

Rituxan and Treanda for CLL

Rituximab has been shown to prolong survival when used with chemotherapy in CLL.
The findings come from a comparative analysis of two completed national phase II and phase III clinical trials. There is insufficient evidence at this time to support or refute the use of single-agent rituximab or a rituximab-containing chemotherapy regimen in patients with chronic lymphocytic leukemia (CLL). Rituxan is not listed by NCCN for CLL as a single agent, except in the elderly.

Treanda is now FDA approved. A study of with Treanda (bendamustine)published in the Journal of Clinical Oncology in May 2005 showed significant activity of Treanda and Rituxan® (Rituximab) for the treatment of relapsed or refractory low-grade NHL or mantle cell lymphoma. A multicenter U.S. and Canadian trial of Treanda evaluated Treanda in combination with Rituxan in 67 patients with indolent or mantle cell lymphoma who had failed chemotherapy was presented at ASH 2005. Thirty-seven per cent had also failed Rituxan. The overall response rate was 87% with complete responses observed in 33%. The most frequent complications were related to reversible myelotoxicity.

On October 31, 2008, the U.S. Food and Drug Administration (FDA) approved bendamustine hydrochloride (TREANDA®, Cephalon, Inc.), an intravenously administered alkylating agent, for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Putting the two drugs together is still in studies but the regimen already has guideline support. In a Phase II clinical trial, the combination of Treanda® (bendamustine) and Rituxan® (rituximab) produced promising results among patients with relapsed chronic lymphocytic leukemia (CLL). These results were presented at the 50th Annual Meeting of the American Society of Hematology.These results have led to a new trial comparing the efficacy of Treanda and Rituxan to Fludara® (fludarabine), Cytoxan® (cyclophosphamide) and Rituxan for treatment of newly diagnosed patients, NCT00769522. This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia. In this study, Treanda and Rituxan are the standard arm.

German researchers have also performed a randomized trial comparing BOP (bendamustine, oncovin and prednisone) to COP (cyclophosphamide, oncovin and prednisone) in a randomized trial of 513 patients with untreated indolent and mantle-cell lymphoma who were randomly assigned to bendamustine/rituximab (BR) or R-CHOP, and the initial results were presented at the 2009 American Society of Hematology annual meeting. All patients with FL (N = 279, median age 60) had defined indications for treatment. The overall response rate with BR was 93%, and the complete response rate and progression-free survival were superior to those seen with R-CHOP
The 2011 NCCN treatment guideline recommends the following:

•Treanda as a single agent as initial therapy for CLL
•Treanda as a single agent or in combination with Rituxan® (rituximab) for treatment of CLL that has recurred following prior therapy (second-line therapy.

•Treanda with or without Rituxan as first-line therapy for follicular lymphoma or mantle-cell lymphoma (p.FOLL-B) and this is a category 1 recommendation.

Kath R, Blumenstengel K, Fricke HJ, Höffken K (January 2001). "Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia". J. Cancer Res. Clin. Oncol. 127 (1): 48–54

Robinson KS, Williams ME, Cohen P, et al. Bendamustine HCL (TREANDA) plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin’s lymphoma: a phase II study. Blood. 2005;106:271a, abstract # 923.

Friedberg JW, Cohen P, Cheson BD, et al. Bendamustine HCL (Treanda) results in high rate of objective response in patients with rituximab-refractory and alkylator-refractory indolent B-cell non-Hodgkin’s lymphoma (NHL): results from a phase II multicenter single-agent study (SDX-105-01). Blood . 2005;106:70a, abstract # 229.

Imrie K, Stevens A, Meyer R, Hematology Disease Site Group. Rituximab in lymphoma and chronic lymphocytic leukemia: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Dec 22. 46 p. (Evidence-based series; no. 6-8). [65 references]

W. G. Wierda Current and Investigational Therapies for Patients with CLL
Hematology, January 1, 2006; 2006(1): 285 - 294.

Huhn D, von Schilling C, Wilhelm M, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood. 2001;98:1326–1331.

Fischer K, Stilgenbauer S, Schweighofer CD et al. Bendamustine in combination with rituximab (BR) for patients with relapsed chronic lymphocytic leukemia (CLL): a multicentre phase II trial of the German CLL Study Group (GCLLSG). Presented at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2008. Abstract 330.

FDG PET of HCC

The detection rate of hepatocellular carcinoma in FDG (fluorodeoxy glucose)-PET is 50 to 70%, and it is inferior to that in ultrasonic testing and computed tomograph. Since dephosphorization enzymatic activity is high in hepatocellular carcinoma, especially of highly-differentiated type, the FDG is pumped out of the cells. Studies seem to peg sensitivity of FDG PET for detection of HCC at the unacceptable 50%, though it is higher for less differentiated cancers. This is lower than CT, MRI and even ultrasound11C-acetate PET is being studied for this cancer for this reason.

BASL Guideline says: "The usefulness of positron emission tomography (PET scan) is not established in HCC."

 

Chi-Lai Ho, Simon C.H. Yu, and David W.C. Yeung11C-Acetate PET Imaging in Hepatocellular Carcinoma and Other Liver Masses  J Nucl Med 44: 213-221.

J.-W. Park, J. H. Kim, S. K. Kim, K. W. Kang, K. W. Park, J.-I. Choi, W. J. Lee, C.-M. Kim, and B. H. Nam
A Prospective Evaluation of 18F-FDG and 11C-Acetate PET/CT for Detection of Primary and Metastatic Hepatocellular Carcinoma
J. Nucl. Med., December 1, 2008; 49(12): 1912 - 1921.

Y-x He and Q-y Guo
Clinical applications and advances of positron emission tomography with fluorine-18-fluorodeoxyglucose (18F-FDG) in the diagnosis of liver neoplasms
Postgrad. Med. J., May 1, 2008; 84(991): 246 - 251.

Salvage gemcitabine and oxaliplatin with Rituxan for mantle lymphoma

Mantle cell lymphoma is a fairly recently identified subtype of non-Hodgkin's lymphoma. Regarded as a low-grade tumour in previous classifications, it has a median survival of only 36 months and is incurable by current treatment approaches. Widespread disease is usually present at diagnosis involving lymph nodes, spleen, bone marrow and extranodal sites such as the gastrointestinal tract. Initial response rates to treatment are high but the majority of patients relapse within 2 years. There is some evidence that high dose myeloablative chemotherapy and total body irradiation followed by stem cell rescue in first remission may give long-term disease-free survival. Both rituximab and Velcade are being clinically investigated as a part of induction. A recent study that used Rituxan reported good results in comparison with historical controls.

Rituximab, gemcitabine and oxaliplatin are active as single agents in relapsed or refractory lymphoma. In a recent study of the combination of the three drugs, forty-six patients with relapsed or refractory B-cell lymphoma received up to eight cycles of R-GemOx (rituximab 375 mg/m2 on day 1, gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 on day 2). The majority (72%) had diffuse large B-cell lymphoma. High CR/CRu rates were observed in all histological subtypes. In patients who had previously received rituximab, the CR/CRu rate after eight cycles was 65%. The 2-year event-free and overall survival rates (median follow-up of 28 months) were 43% and 66%, respectively. Among responders, the probability of being disease free for 2 years was 62%. Treatment was generally well tolerated. The treatmetn is still udner study: Rituximab, Gemcitabine and Oxaliplatin (R-GEMOX)for Refractory/Relapsed B-Cell Lymphoma, NCT00169195

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

Imrie K, Stevens A, Meyer R, Hematology Disease Site Group. Rituximab in lymphoma and chronic lymphocytic leukemia: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Dec 22. 46 p. (Evidence-based series; no. 6-8). [65 references]

El Gnaoui , J Dupuis , K Belhadj , J-P Jais , A Rahmouni , C Copie-Bergman , I Gaillard , M Diviné , I Tabah-Fisch , F Reyes , and C Haioun Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy Annals of Oncology. Ann Oncol 18: 1363-1368.

Taxotere and gemcitabine for bladder cancer

A variety of therapeutic options are available to patients with recurrent bladder cancer. Recent studies have suggested that the combination of Gemzar® and Platinol® represents the optimal current combination for treatment of advanced or metastatic bladder cancer.  This patient received this combination but more than a yearago.

Less is known about how to deal with recurrent metastatic disease. NCCN says: "No standard therapy exists in this setting. Options include single agent therapy with a taxane or premetrexed...".In one trial, docetaxel and gemcitabine combination therapy in patients with progressing regional or metastatic transitional cell carcinoma who had failed a prior chemotherapy treatment. Five patients obtained an objective response for an overall response rate of 17% (90% confidence interval, 7-33%). One patient achieved a complete clinical response. The median overall survival of the group was 7.7 months.The authors concluded that for patients who have failed a previous chemotherapy regimen, this gemcitabine-docetaxel combination may be a useful alternative; however, it was obviously not a very active regimen.

NCCN.ORG, Bladder cancer Manola JB, Dreicer R, Wilding G. Gemcitabine and docetaxel in advanced carcinoma of the urothelium: report of a phase II Eastern Cooperative Oncology Group trial. Program and abstracts of the American Society of Clinical Oncology 38th Annual Meeting, May 18-21, 2002; Orlando, Florida. Abstract 796

Dreicer R, Manola J, Schneider DJ, Schwerkoske JF, George CS, Roth BJ, Wilding G; Eastern Cooperative Oncology Group. Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group.Cancer. 2003 Jun 1;97(11):2743-7. Galsky, Matthew D. The Role of Taxanes in the Management of Bladder Cancer Oncologist 2005 10: 792-798

Galsky, Matthew D.
The Role of Taxanes in the Management of Bladder Cancer
Oncologist 2005 10: 792-798