Cancer Treatment

CT scanning for malignancy in dermatomyositis

Dermatomyositis is an autoimmune  disease that has a characteristic skin eruptionand may be  autoimmune; it is sometimes associated with malignancy. Because this is a rare disease, not much is known about this association and there are no guidelines to my knowledge, but experts often recommend CT scanning to exclude coexistent malignancy. In one retropsectove review, malignancy ocurred in 16 of 4o patients.

Agnès Sparsa, Eric Liozon, François Herrmann, Kim Ly, Valérie Lebrun, Pascale Soria, Véronique Loustaud-Ratti, Marie-Laure Bouyssou-Gauthier, Serge Boulinguez, Christophe Bédane, Marie-Odile Jauberteau, Elisabeth Vidal, and Jean-Marie Bonnetblanc
Routine vs Extensive Malignancy Search for Adult Dermatomyositis and Polymyositis: A Study of 40 Patients
Arch Dermatol, Jul 2002; 138: 885 - 890.

Scheinfeld N. A review of the cutaneous paraneoplastic associations and metastatic presentations of ovarian carcinoma. Clin Exp Dermatol.2008 Jan;33(1):10-5. Epub 2007 Nov 3. (s)

 

Beclomethasone for graft versus host disease

The pathological and clinical findings of gastrointestinal (GI) graft-versus-host disease (GVHD) are similar to those of inflammatory bowel disease. Three previous studies had shown the safety and efficacy of the topical BDP for GI GVHD. It is possibe that it would function similarly for GVHD. Several small pahse IIs tudies suggest that it suppresses allogeneic immune responses in the gut without causing significant immunosuppression.

This therapy is under study: Compassionate Use of Beclomethasone in Treating Patients With Graft-Versus-Host Disease of the Gastrointestinal Tract, NCT00055666.

G.McDonald, M.Bouvier, D.Hockenbery, J.Stern, T.Gooley, A.Farrand, C.Murakami, D.Levine
Oral beclomethasone dipropionate for treatment of intestinal graft-versus-host disease: A randomized, controlled trial Gastroenterology, Volume 115, Issue 1, Pages 28-35

Y Miura et al, Oral beclomethasone dipropionate as an initial treatment of gastrointestinal acute graft-versus-host disease after reduced-intensity cord blood transplantation Bone Marrow Transplantation (2006) 38, 577–579.

Extragonadal germ cell tumors: role of transplant

High dose chemotherapy with autologous stem cell rescue is an accepted and standard of care approach for relapsed or nonresponding testicular cancer. It is recommended by several guidelines, including NCCN.

Extragonadal germinal cell syndromes are rare tumors that predominantly affect young males. Histologically, they mirror their gonadal counterparts with which they share the same chemosensitivity and radiosensitivity. Controversy remains regarding the origin of extragonadal germ cell tumors (EGGCTs). The classic theory suggests that germ cell tumors (GCTs) in these areas are derived from local transformation of primordial germ cells misplaced during embryogenesis but a recent alternative theory suggests that primary mediastinal presentations represent reverse migration of occult carcinoma in situ (CIS) lesions in the gonad; hence, they may be gonadal in origin. Some retroperitoneal extragonadal germ cell tumors may represent metastases from a testicular cancer, with subsequent spontaneous necrosis of the primary tumour.

For patients receiving intensive chemotherapy, 5-year survival rates of 40-65% have been reported.The mediastinum is the most common site of extragonadal germ cell tumors. Mediastinal germ cell tumors account for only 2-5% of all germinal tumors, but they constitute 50-70% of all extragonadal tumors. Treatment with 4 cycles of bleomycin, etoposide, and cisplatin (BEP) is the current standard of care. Radiotherapy or surgery can be used after chemotherapy in bulky mediastinal seminomas. Among those whose disease relapses after or progressed on first-line chemotherapy, or those in high risk, or whose disese could not be resected, surgery shuld be attmepted. Otherwise, it is rare to achieve complete remission despite salvage therapy with cisplatin-based regimens, high-dose chemotherapy, paclitaxel, or oral etoposide. High dose therapy is the best hope for these patients, but it is not yet etablished and continues to be investigated, for example: Paclitaxel, Ifosfamide, and Carboplatin Followed By Autologous Stem Cell Transplant in Treating Patients With Germ Cell Tumors That Did Not Respond to Cisplatin, NCT00423852.

A randomized controlled trial compared conventional doses of salvage chemotherapy to high-dose chemotherapy with autologous marrow rescue in 263 patients with recurrent or refractory germ cell tumors. Of the 263 patients, 43 of whom had extragonadal primary tumors, more toxic effects and treatment-related deaths were seen in the high-dose arm without any improvement in response rate or overall survival. One would have to consider transplantation as investigational at this time for this disease.

H. J. Schmoll, R. Souchon, S. Krege, P. Albers, J. Beyer, C. Kollmannsberger, S. D. Fossa, N. E. Skakkebaek, R. de Wit, K. Fizazi, et al.
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)
Ann. Onc., September 1, 2004; 15(9): 1377 - 1399.

H. J. Schmoll, R. Souchon, S. Krege, P. Albers, J. Beyer, C. Kollmannsberger, S. D. Fossa, N. E. Skakkebaek, R. de Wit, K. Fizazi, et al.
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)
Ann. Onc., September 1, 2004; 15(9): 1377 - 1399.

Pico JL, Rosti G, Kramar A, et al.: A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 16 (7): 1152-9, 2005. 

Gemcitabine and Taxol for breast cancer

A phase III trial of front-line therapy with gemcitabine plus paclitaxel compared with paclitaxel alone for the treatment of women with metastatic breast cancer revealed that the combination is superior for overall survival as well as prevention of disease progression. The one-year survival rate for gemcitabine plus paclitaxel was 70.7% compared with 60.9% for paclitaxel (P = .019). The adjusted hazard ratio for combined therapy was 0.74 (P = .006). The U.S. Food and Drug Administration approved gemcitabine (Gemzar) for use in metastatic breast cancer on May 19, 2004 based on this study. It is guideline recommended afer first line as a single agent.

This regimen would be appropriate for first line and may be considered appropriate for subsequent lines, when taxanes have not been previously used. The combination of the three drugs is in a phase II study: A Study of Biweekly Gemcitabine, Paclitaxel, and Avastin in Patients With Metastatic Breast Cancer,
NCT00618826 (This study has been suspended. Pending Modification )

guidance.nice.org.uk/TA116

National Institute for Health and Clinical Excellence (NICE). Gemcitabine for the treatment of metastatic breast cancer. London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Jan. 24 p. (Technology appraisal guidance; no. 116).

Dent S, Messersmith H, Trudeau M, Breast Cancer Disease Site Group. The role of gemcitabine in the management of metastatic breast cancer: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2007 Jan 22. 5 p. (Evidence-based series; no. 1-12). [11 references]

Carlos Delfino at al, Gemcitabine plus Paclitaxel as First-Line Chemotherapy for Patients with Advanced Breast Cancer Oncology Vol. 66, No. 1, 2004

Metastatic anal cancer

Metastatic anal cancer is not well studied in regard to chemo options for metastatic disease. NCCN recommends only 5FU and cisplatin or cisplatin for metastatic anal cancer A recent review states: ". Metastatic disease develops in 10%–17% of patients treated with chemoradiation therapy. The most common site of distant metastasis is the liver. There are limited published data on the use of chemotherapy, particularly newer agents, to treat metastatic anal carcinoma. Active agents include cisplatin plus 5-FU, carboplatin, doxorubicin, and semustine. Participation in a clinical trial should be discussed with all potentially eligible patients. "

I was not able to find credible literature supporting the use of Xeloda in this setting.Erbitux is a drug that is active in many different cancer typoes, both adenocarcinomas, f.e. of colon, and squamous, such as in head and neck. However, less is known about its rule for treatment of anal cancer or its role in combination with 5Fu, especially in the metastatic setting ( several combination therapies are lsited as being clinical trials for localized disease). NCCN lists only 5 Fu and cisplatin for metastatic anal cancer therapy.

 Principles and Practice of Gastrointestinal Oncology (Hardcover)
by David P Kelsen (Editor), John M Daly (Editor), Scott E Kern (Editor), Bernard Levin Editor), Joel E Tepper (Editor) Publisher: Lippincott Williams & Wilkins; Second Edition edition (October 1, 2007), p.648
ISBN-13: 978-0781776172

nccn.org, anal cancer

American College of Radiology (ACR), Expert Panel on Radiation Oncology-Rectal/Anal Cancer. Anal cancer. Reston (VA): American College of Radiology (ACR); 2002. 11 p. (ACR appropriateness criteria). [31 references]

NCCN.ORG, Anal Cancer

Abeloff: Clinical Oncology 3rd Ed.-2004 , Ch. 82

Uronis, Hope E. , Bendell, Johanna C.
Anal Cancer: An Overview
Oncologist 2007 12: 524-534

American College of Radiology (ACR), Expert Panel on Radiation Oncology-Rectal/Anal Cancer. Anal cancer. Reston (VA): American College of Radiology (ACR); 2002. 11 p. (ACR appropriateness criteria). [31 references]

NCCN.ORG, Anal Cancer

Abeloff: Clinical Oncology 3rd Ed.-2004 , Ch. 82

Uronis, Hope E. , Bendell, Johanna C.
Anal Cancer: An Overview
Oncologist 2007 12: 524-534

Torisel for hepatocellular carcinoma

Temsirolimus is a mTOR inhibitor.  Iti i FDA approved for renal cell carcinoma. The mTOR pathway is activated in 40-50% of patients with hepatocellular cancer (HCC). In different models (i.e., hepatoma cell lines and implanted HCC tumors in rats), mTOR inhibitors (mTORIs) were effective in reducing cell growth and tumor vascularity. Synergistic effects were observed for mTORIs and chemotherapeutic agents in these studies. Clinical data are, as yet, only preliminary and are mainly derived from retrospective studies in patients who underwent liver transplantation for HCC. Those patients had received sirolimus thereafter for immunosuppression, and a much lower rate of tumor recurrence than with calcineurin inhibitors alone was noted. Current prospective trials of MTOR inhibitors are ongoing for treatment of advanced HCC .

A similar drug is in a current trial: Randomized Phase I/II of RAD001 in Advanced Hepatocellular Carcinoma (HCC), NCT00390195

Treiber, Gerhard, mTOR inhibitors for hepatocellular cancer: a forward-moving target
Expert Review of Anticancer Therapy, Volume 9, Number 2, February 2009 , pp. 247-261(15)

P. Newell, A. Villanueva, J. Llovet, Molecular targeted therapies in hepatocellular carcinoma: From pre-clinical models to clinical trials, Journal of Hepatology, Volume 49, Issue 1, Page 1

Josep M. Llovet Novel advancements in the management of hepatocellular carcinoma in 2008
Journal of Hepatology Volume 48, Supplement 1, 2008, Pages S20-S37 Management of Liver Diseases 2008   

Chemo for Choriocarcinoma

Gestational trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta and includes the most agressive type, choriocarcinoma.  Histologically distinct disease entities encompassed by this general terminology include complete and partial hydatidiform moles, invasive moles, gestational choriocarcinomas, and placental site trophoblastic tumors. Before the advent of sensitive assays for human chorionic gonadotropin (hCG) and efficacious chemotherapy, the morbidity and mortality from gestational trophoblastic disease were substantial. In agressive high-risk cases,  aggressive multiagent chemotherapy and individualized multimodality therapy is warranted . At present, treatment with single-agent methotrexate or actinomycin D is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and oncovin) are recommended for intermediate or high-risk disease. A recent guideline says this about the choice of chemotherapy: "•Women with high-risk metastatic disease should be treated with multiagent chemotherapy. This includes triple therapy with methotrexate, dactinomycin, and either chlorambucil or cyclophosphamide. More recent regimens further incorporate etoposide with or without cisplatin into combination chemotherapy.".

Royal College of Obstetricians and Gynaecologists (RCOG). The management of gestational trophoblastic neoplasia. London (UK): Royal College of Obstetricians and Gyneacologists (RCOG); 2004 Feb. 7 p. (Guideline; no. 38). [16 references]

American College of Obstetricians and Gynecologists (ACOG). Diagnosis and treatment of gestational trophoblastic disease. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2004 Jun. 13 p. (ACOG practice bulletin; no. 53). [49 references]

Kufe D (2000). Benedict RC, Holland JF. ed. Cancer medicine (5th ed. ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1.

^Rustin GJ, Newlands ES, Begent RH, Dent J, Bagshawe KD (1989). "Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma". J. Clin. Oncol. 7 (7): 900–3.

Tarceva alone for pancreatic cancer

Erlotinib is an orally administered quinazoline derivative that targets and inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase enzyme, thereby disrupting signalling pathways that encourage cell growth and inhibit apoptosis. There is evidence of in-vitro and cell tissue studies but no human studies that I could discover of this drug effective alone against pancratic cancer. Studies have been in combination with other drugs and in fact, it may not be effective alone.

There is a phase II study ongoing: Phase II Trial of Erlotinib in Advanced Pancreatic Cancer, NCT00497224. This is an open-label, multi-center phase II study of erlotinib in patients with metastatic or locally advanced, unresectable pancreatic cancer who have received up to one line of gemcitabine based chemotherapy.

Laurent-Puig P, Taieb J.Lessons from Tarceva in pancreatic cancer: where are we now, and how should future trials be designed in pancreatic cancer?Curr Opin Oncol. 2008 Jul;20(4):454-8.

Dene Simpson, Lesley J Scott, Stuart NobleErlotinib: In Advanced Pancreatic Cancer
American Journal of Cancer, Vol. 5, No. 1. (2006), pp. 35-40.

Joshua W. Long, Donald J. Buchsbaum, Jeffery Sellers, Zhi Huang, Selwyn M. Vickers Erlotinib Reduces Flip Mediated Resistance to TRA-8 Agonistic TRAIL-R2 Antibody in Pancreatic Cancer Cells nd Journal of Surgical Research, Volume 144, Issue 2, February 2008, Pages 387

PET for staging mesothelioma

Staging is the process of finding out how far the cancer has spread. Staging of mesothelioma is based on imaging studies such as x-rays, CT scans, and MRI scans.

Earlier studies indicate that PET holds great promise for Earlier studies indicate that PET holds great promise for diagnosing mesothelioma and determining mesothelioma staging, or the extent to which tumors have spread. At the University of Pennsylvania Medical Center, researchers evaluated 28 patients for mesothelioma using the sugar tracer fluoro–2–deoxy–D–glucose (FDG) and PET (Chest. 1998 Sep; 114(3): 713–22). In a comparison of PET imaging with thoracoscopy or surgical biopsies, PET successfully indicated the presence of disease in 24 patients, and of benign conditions in the other four. The uptake of FDG was significantly higher in diseased cells, and PET analysis also showed tumors in the lymph nodes of 9 patients. The lymph nodes appeared normal in CT scans. Another study at Brigham and Women’s Hospital and Harvard Medical School in Boston traced 15 patients, 11 of whom had mesothelioma and four who were disease–free. PET results were compared with laboratory analysis of biopsied fluids and tissues. PET detected all 11 primary tumors, and confirmed the absence of disease in the other four patients. Out of 28 disease–positive lesions, PET accurately detected. The exact role, however, is not etablished and I was not able to find any guidelines recommending PET over CT for staging. There are no guidelines that recommend routine PET surveillance of either mesothelioma or metastatic cancer to the pertineunum.

Aaseboe U, Billing B, Bjørck T, Brodin O, Brunsvig P, Forsløw U, Frank H, Hansen O, Harving H, Hillerdal G, Jakobsen KD, Johansson A, Ladegaard L, Lindh B, Melgaard P, Mygind N, Månsson T, Palshof T, Sundstrøm S, Sørensen P, Vigander T. Preoperative staging of mesothelioma by 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography fused imaging and mediastinoscopy compared to pathological findings after extrapleural pneumonectomy European Journal of Cardio-Thoracic Surgery. 2008 Nov;34(5):1090-6. Epub 2008 Sep 16.

Gerbaudo VH, Sugarbaker DJ, Britz-Cunningham S, Di Carli MF, Mauceri C, Treves ST. Assessment of malignant pleural mesothelioma with (18)F-FDG dual-head gamma-camera coincidence imaging: comparison with histopathology.Nucl Med. 2002 Sep;43(9):1144-9

Hinshaw JL, Pickhardt PJ. Imaging of primary malignant tumors of peritoneal and retroperitoneal origin Cancer Treatment and Research. 2008;143:281-97.

MUGA before and during chemotherapy

The MUGA scan (MUltiple Gated Acquisition scan) is a noninvasive tool for assessing the function of the heart. The MUGA scan produces a moving image of the beating heart, and from this image several important features can be determined about the health of the cardiac ventricles (the heart’s major pumping chambers) and a measurement of cardiac ejection fraction. The latter can be monitored during chemotherapy to diagnos cardiotoxicity and adjust chemo, is it is noted.

Guidelines recommend routine use of MUGA before the administration of doxorubicin for adjuvant therapy for breast cancer but this  has recently been questioned. Nevertheless, serial MUGA scans are widely recommended and are standard of care at this time.

Sabel, Michael S.; Levine, Ellis G.; Hurd, Thelma; Schwartz, Gary N.; Zielinski, Robert; Hohn, David; Edge, Stephen B.Cancer Management Controversy
Is MUGA Scan Necessary in Patients With Low-Risk Breast Cancer Before Doxorubicin-Based Adjuvant Therapy?American Journal of Clinical Oncology: Cancer Clinical Trials:
August 2001 - Volume 24 - Issue 4 - pp 425-428

Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer. 2002;95:1592-1600.

Breast Cancer: Prognosis, Treatment, and Prevention [ILLUSTRATED] (Hardcover)
by Jorge R. Pasqualini (Editor)
Informa Healthcare; 1 edition (July 17, 2002)
ISBN-13: 978-0824707125