Cancer Treatment Today » Anal Cancer

Cisplatin and Xeloda for metastatic anal cancer – pro

M Levin, MD — Fri, 14 Sep 2012 16:09:02 +0000

Systemic chemotherapy remains the mainstay of treatment for patient with metastatic anal cancer. The National Comprehensive Cancer Network (NCCN) Guidelines currently recommend cisplatin and 5FU chemotherapy as first-line treatment of metastatic squamous cell carcinoma (SCC). This is largely based on a study of 19 patients treated with cisplatin 100 mg/m2 and infusional 5FU 1 gm/m2/day over 5 days with a 66% response rate; there was 1 complete response and 11 partial responses in addition to 4 patients with stable disease. The actuarial survival was 62.2% at 1 year and 32.2% at 5 years, and the median survival was 34.5 months]. There have also been a number of case reports demonstrating a benefit with the cisplatin/5FU combination. This is the best researched, although not extensively supported, regimen for anal cancer.

Recently the oral fluoropyrimidine capecitabine(Xeloda) has been substituted for 5FU in a number of solid tumours, and, extrapolating from this data, many oncologists use capecitabine with cisplatin rather than 5FU. This has a number of advantages for patients, including ease of administration and possibly greater efficacy. Unfortunately, however, there is no literature support for this substitution.

D. Cunningham, N. Starling, S. Rao et al., “Capecitabine and oxaliplatin for advanced esophagogastric cancer,” New England Journal of Medicine, vol. 358, no. 1, pp. 36–46, 2008.

P. Pfeiffer, J. P. Mortensen, B. Bjerregaard et al., “Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer,” European Journal of Cancer, vol. 42, no. 16, pp. 2738–2743, 2006.

Alice Dewdney and Sheela Rao Metastatic Squamous Cell Carcinoma of the Anus: Time for a Shift in the Treatment Paradigm? ISRN OncologyVolume 2012 (2012)

NCCN, Anal -6, 2012

See Lay version here

Adjuvant therapy for anal cancer – pro

M Levin, MD — Thu, 06 Sep 2012 16:06:24 +0000

Anal cancer is a rare clinical entity which represents 1–2% of all gastrointestinal tract cancers. Due to the paucity of this malignancy it has been difficult to establish generally accepted guidelines for treatment, although various therapy modalities have been evaluated. For a long time radical surgery was the primary treatment for anal cancer and still about 30% of the patients undergo abdominoperineal rectotomy. However, recurrence rates of 20–40% have been observed after this multilating procedure. Therefore, other treatment options, including external or interstitial radiotherapy and chemotherapy, are used increasingly with the intention to preserve sphincter function. In the last years much interest has been addressed to multimodal therapy with radiation (50 Gy) and chemotherapy (5 fluouracil and mitomycin C). Presently radiochemotherapy appears to be the most efficient therapy in advanced anal cancer. Locoregional tumor control is obtained in 60–80% of the patients and there is evidence that radiochemotherapy can improve disease-free survival. The combination of 5-FU/mitomycin-C and radiation has demonstrated durable rates of local control but no benefit to overall survival. In a trial from the European Organization for Research and Treatment of Cancer (EORTC), patients were randomized to receive radiotherapy alone (45 Gy over 5 weeks) or radiotherapy and chemotherapy with 5-FU/ mitomycin-C. Patients in the combined modality arm had decreased rates of local recurrence. Current recommendations for treatment are based on this EORTC trial. Giving 5 FU alone is reasonable in the elderly patients, based on phase II trials.

nccn.org, Anal cancer

N Charnley et al, Effective treatment of anal cancer in the elderly with low-dose chemoradiotherapy British Journal of Cancer (2005) 92, 1221-1225.

Dennis L. Rousseau et al, Overview of anal cancer for the surgeon Surgical Oncology Clinics of North America Volume 13, Issue 2, April 2004, Pages 249-262

Erbitux for anal cancer – pro

admin — Sat, 01 Sep 2012 22:37:23 +0000

There is limited evidence for activity of irinotecana dn Erbitux for emtastatic squamous cell cancer of the anus. One is a case report of a a female patient with refractory anal cancer who achieved an excellent response to the combination of cetuximab and irinotecan after having failed single-agent irinotecan. The other is a report on 7 patients with metastatic anal cancer treated with cetuximab – a chimeric antibody against EGFR – on a compassionate use basis along with the results of KRAS mutational analysis. Marked tumor shrinkage was noted in several patients using cetuximab monotherapy or cetuximab/irinotecan combination as first or subsequent treatment line (usually after failure of cisplatin-based regimens). Two out of seven patients harbored KRAS mutations. Both patients had progressive disease receiving cetuximab, while the remaining 5 patients had either a partial remission (n = 3), a minor remission (n = 1) or no change lasting 6 months after previous rapid tumor progression.

Both are preliminary communications and no prospective studies have yet been done. This is an intriguing but still experimental therapy for anal carcinomas.

EPhan, Lan K. M.P.A.S., P.A.-C.; Hoff, Paulo M. M.D., F.A.C.P.
Evidence of Clinical Activity for Cetuximab Combined with Irinotecan in a Patient with Refractory Anal Canal Squamous-Cell Carcinoma: Report of a Case
Diseases of the Colon & Rectum:
doi: 10.1007/s10350-006-0786-9

Nadine Lukan et al, Cetuximab-Based Treatment of Metastatic Anal Cancer: Correlation of Response with KRAS Mutational Status Oncology Vol. 77, No. 5, 2009

Decitabine and epigenetic therapy for solid cancers – pro

M Levin, MD — Wed, 22 Aug 2012 20:41:15 +0000

Lay search: Decitabine is being studies for “epigenetic” therapy of solid cancers.

Genes involved in all aspects of tumor development and growth can become aberrantly methylated in tumor cells, including genes involved in apoptosis and cell cycle regulation. Decitabine, 2´-deoxy-5-azacytidine, can inhibit DNA methyltransferases and reverse epigenetic silencing of aberrantly methylated genes. Nucleoside DNA methyltransferase inhibitors, such as decitabine, have been reported to have antitumor activity, especially against hematologic malignancies. Such demethylating agents have been proposed to reactivate tumor suppressor genes aberrantly methylated in tumor cells, leading to inhibition of tumor growth.

Currenlty Decitabine is FDA approved for myedlodysplaisa. Because of the aforementioned mechanism of action, there is interest in studying it in colorectal and other solid cancers. Decitabine has been studied in several phase II trials for solid tumours as well as in different types of leukaemia. The drug has been shown to have very limited efficacy against solid tumours. However, decitabine exhibits higher activity for the treatment of haematological malignancies.

Robert Brown, Jane A Plumb Demethylation of DNA by decitabine in cancer chemotherapyExpert Review of Anticancer Therapy August 2004, Vol. 4, No. 4, Pages 501-510

Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.

Kantarjian H, O’Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.

http://jco.ascopubs.org/cgi/reprint/JCO.2004.01.947v1.pdf

Adis Decitabine: 2′-Deoxy-5-azacytidine, Aza dC, DAC, Dezocitidine, NSC 127716. R&D Profile Drugs in R & D. 4(6):352-358, 2003.

Jean-Pierre J. Issa DNA Methylation as a Therapeutic Target in Cancer Clinical Cancer Research 13, 1634-1637, March 15, 2007.

Metastatic anal cancer – pro

M Levin, MD — Wed, 22 Aug 2012 20:34:16 +0000

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. ESMO 2014 lists and mildly approves of single agent therapies second line.

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

Hainsworth, J.D., et al., Paclitaxel, carboplatin, and long-term continuous infusion of 5-fluorouracil in the treatment of advanced squamous and other selected carcinomas: results of a Phase II trial. Cancer, 2001. 92(3): p. 642-9.

NCCN.ORG, Anal Cancer 2012

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

PET for anal cancer: anal canal versus anal margin – pro

M Levin, MD — Wed, 22 Aug 2012 20:31:50 +0000

Anal canal cancer metastasize more to the iliac nodes and of anal margin go more to the inguinal nodes. A recent review found that the accuracy of PET scan was poor for anal cancer even with palpable inguinal nodes. PET scan sensitivity was 50%, specificity = 72%, predictive value positive (PVP) = 50%, predictive value negative = 80%. 64% of scans were performed within 6 months of treatment; in these, PVP = 33% and PVN = 66%. PET scanning for anal SCC provides accurate staging of disease at presentation and may alter treatment planning by identifying inguinal node involvement not apparent on clinical examination. In this series, PET scan results did not change post-chemoradiation management in any case. Importantly, resolution of primary tumor defined by PET scan was accurate only 80% of the time. PE and Bx within 3 months of treatment were more accurate than PET scan in assessing disease. This review concludes that : “Post-treatment evaluation of anal SCC should continue to include careful PE, CT scan and Bx when appropriate”. however, this review did not distinguish between anal canal and anal margin cancers. Most cases appear to have been anal margin.

NCCN lists PETfor the initial staging of anal canal (as in our case) but not for anal margin cancer prior to 5FU/Mitomycin and radiation. A guideline says of anal canal cancer: “Positron emission tomography (PET) scanning may have a role as an adjunct to CT of the pelvis, abdomen, and chest, identifying sites of metastasis not observed on CT in 25 percent of cases. Almost 20 percent of patients with inguinal nodes that are negative by both physical examination and CT scan are positive on PET. This has prognostic significance and may influence the radiation treatment plan.”

In conclusion, PET appears to be well established prior to but not after chemoradiation. False positives would be expected to be much higher after chemoradiation.

Fleshner PR, Chalasani S, Chang GJ, Levien DH, Hyman NH, Buie WD, Standards Practice Task Force of the American Society of Colon and Rectal Surgeons. Practice parameters for anal squamous neoplasms. Dis Colon Rectum 2008 Jan;51(1):2-9.

Nagle, D., Henry, D., Iagaru, A., Mastoris, J., Chmielewski, L., Rosenstock, J. The utility of PET scanning in the management of squamous cell carcinoma of the anus J Clin Oncol (Meeting Abstracts) 2006 24: 4152

nccn.org, anal 2012, ANAL-3

Erbitux for anal cancer – pro

M Levin, MD — Wed, 22 Aug 2012 20:27:43 +0000

Both are preliminary communications and no prospective studies have yet been done. This is an intriguing but still experimental therapy for anal carcinomas.

EPhan, Lan K. M.P.A.S., P.A.-C.; Hoff, Paulo M. M.D., F.A.C.P.
Evidence of Clinical Activity for Cetuximab Combined with Irinotecan in a Patient with Refractory Anal Canal Squamous-Cell Carcinoma: Report of a Case Diseases of the Colon & Rectum: doi: 10.1007/s10350-006-0786-9

Nadine Lukan et al, Cetuximab-Based Treatment of Metastatic Anal Cancer: Correlation of Response with KRAS Mutational Status Oncology Vol. 77, No. 5, 2009

Combined Resection for Anal Cancer – pro

M Levin, MD — Fri, 03 Aug 2012 13:19:18 +0000

While a combined resection of rectal cancer and partial hepatectomy are well established, the same is not the case for anal cancer. Metastatic anal cancer is not well studied in regard to combined resection. 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.”

Although there have been no randomized trials comparing surgery with radiation treatment or with combined chemoradiation, based on multiple studies and clinical experience for the last 20 years, there has been a substantial change in the management of epidermoid anal carcinomas, with more patients undergoing nonsurgical treatment.

I was not able to find credible literature supporting a combined resection approach for anal cancer. NCCN lists only 5 Fu and cisplatin for metastatic anal cancer therapy. The first report of this approach was by Tokar in 2006.

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 2012

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

Tokar M, Bobilev D, Zalmanov S, Geffen DB, Walfisch S. Combined multimodal approach to the treatment of metastatic anal carcinoma: report of a case and review of the literature. Onkologie. 2006 Feb;29(1-2):30-2.

Read the Layperson version here.