Difference between revisions of "Anal cancer"
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===References=== | ===References=== | ||
# Faivre C, Rougier P, Ducreux M, Mitry E, Lusinchi A, Lasser P, Elias D, Eschwege F. [5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer]. Bull Cancer. 1999 Oct;86(10):861-5. [http://www.jle.com/en/revues/medecine/bdc/e-docs/00/01/12/15/resume.phtml link to original article & English summary] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10572237 PubMed] | # Faivre C, Rougier P, Ducreux M, Mitry E, Lusinchi A, Lasser P, Elias D, Eschwege F. [5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer]. Bull Cancer. 1999 Oct;86(10):861-5. [http://www.jle.com/en/revues/medecine/bdc/e-docs/00/01/12/15/resume.phtml link to original article & English summary] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10572237 PubMed] | ||
+ | # '''Abstract:''' Sclafani F et al. [InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease]. Journal of Clinical Oncology. 2015 33:3_suppl, TPS792-TPS792. [https://ascopubs.org/doi/abs/10.1200/jco.2015.33.3_suppl.tps792 link to abstract] '''contains protocol''' [https://clinicaltrials.gov/ct2/show/NCT02051868 clinicaltrials.gov] | ||
+ | |||
+ | ==Carboplatin & Paclitaxel {{#subobject:1a2b3c|Regimen=1}}== | ||
+ | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
+ | |- | ||
+ | |[[#top|back to top]] | ||
+ | |} | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV on days 1, 8, 15 | ||
+ | |||
+ | '''28-day cycles''' | ||
+ | |||
+ | {| class="wikitable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 25%"|Study | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 25%"|Comparator | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[https://ascopubs.org/doi/abs/10.1200/jco.2015.33.3_suppl.tps792 Sclafani et al. 2017] | ||
+ | | style="background-color:#1a9851" |Randomized Phase II (C) | ||
+ | |Cisplatin & 5-FU | ||
+ | |Not reported | ||
+ | |- | ||
+ | |} | ||
+ | |||
+ | ===References=== | ||
# '''Abstract:''' Sclafani F et al. [InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease]. Journal of Clinical Oncology. 2015 33:3_suppl, TPS792-TPS792. [https://ascopubs.org/doi/abs/10.1200/jco.2015.33.3_suppl.tps792 link to abstract] '''contains protocol''' [https://clinicaltrials.gov/ct2/show/NCT02051868 clinicaltrials.gov] | # '''Abstract:''' Sclafani F et al. [InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease]. Journal of Clinical Oncology. 2015 33:3_suppl, TPS792-TPS792. [https://ascopubs.org/doi/abs/10.1200/jco.2015.33.3_suppl.tps792 link to abstract] '''contains protocol''' [https://clinicaltrials.gov/ct2/show/NCT02051868 clinicaltrials.gov] | ||
Revision as of 14:55, 30 April 2019
Page editor | Section editor | ||
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Ari Seifter, MD University of Illinois at Chicago Chicago, IL |
Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL |
9 regimens on this page
13 variants on this page
|
Guidelines
ESMO
- Anal cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
Definitive chemoradiotherapy for locally advanced disease
Capecitabine, Mitomycin, RT
back to top |
Regimen
Study | Evidence |
---|---|
Glynne-Jones et al. 2008 | Phase II |
Chemoradiotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on radiation days
- Mitomycin (Mutamycin) 12 mg/m2 IV once on day 1
- Concurrent radiation therapy: 1.8 Gy per day x 28 fractions (total dose: 50.4 Gy)
6-week course
References
- EXTRA: Glynne-Jones R, Meadows H, Wan S, Gollins S, Leslie M, Levine E, McDonald AC, Myint S, Samuel L, Sebag-Montefiore D; National Cancer Research Institute Anal Sub Group and Colorectal Clinical Oncology Group. EXTRA--a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):119-26. Epub 2008 May 9. link to original article contains protocol PubMed
Cisplatin, Fluorouracil, RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ajani et al. 2008 (RTOG 98-11) | Phase III (E) | Fluorouracil, Mitomycin, RT | Seems to have inferior OS (*) |
Peiffert et al. 2012 (ACCORD 03) | Non-randomized portion of RCT | ||
James et al. 2013 (ACT II) | Phase III (E) | Fluorouracil, Mitomycin, RT | Seems not superior |
Included for reference purposes only. Efficacy for RTOG 98-11 based on the 2012 update.
Chemoradiotherapy
References
- RTOG 98-11: Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett C. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008 Apr 23;299(16):1914-21. link to original article contains verified protocol PubMed
- Update: Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012 Dec 10;30(35):4344-51. Epub 2012 Nov 13. link to original article link to PMC article PubMed
- ACCORD 03: Peiffert D, Tournier-Rangeard L, Gérard JP, Lemanski C, François E, Giovannini M, Cvitkovic F, Mirabel X, Bouché O, Luporsi E, Conroy T, Montoto-Grillot C, Mornex F, Lusinchi A, Hannoun-Lévi JM, Seitz JF, Adenis A, Hennequin C, Denis B, Ducreux M. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol. 2012 Jun 1;30(16):1941-8. Epub 2012 Apr 23. Erratum in: J Clin Oncol. 2012 Nov 1;30(31):3903. link to original article PubMed
- ACT II: James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial. Lancet Oncol. 2013 May;14(6):516-24. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
Fluorouracil, Mitomycin, RT
back to top |
Variant #1, 3750/15/45
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bartelink et al. 1997 | Phase III (E) | Radiation | Superior local failure rate |
Note: mitomycin is only given with cycle 1.
Chemoradiotherapy
- Fluorouracil (5-FU) 750 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m2)
- Mitomycin (Mutamycin) as follows:
- Cycle 1: 15 mg/m2 IV bolus once on day 1
- Cycle 2: none
- Concurrent radiation therapy: 1.8 Gy x 25 fractions (total dose: 45 Gy)
28-day cycle for 2 cycles
Variant #2, 4000/10/45
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Flam et al. 1996 | Phase III (C) | 5-FU & RT | Superior DFS |
Ajani et al. 2008 (RTOG 98-11) | Phase III (C) | Fluorouracil, Cisplatin, RT | Seems to have superior OS (*) |
Note: efficacy for RTOG 98-11 is based on the 2012 update.
Chemoradiotherapy
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
- Mitomycin (Mutamycin) 10 mg/m2 (maximum dose of 20 mg) IV bolus once on day 1
- Concurrent radiation therapy; at a minimum: 1.8 Gy per day x 25 fractions (total dose: 45 Gy), given over 5 weeks; see articles for additional details
28-day cycle for 2 cycles
Variant #3, 4000/12/45
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Northover et al. 1996 (ACT I) | Phase III (E) | Radiation | Superior local failure rate |
Because there were a few different schedules used in UKCCCR Anal Cancer Trial Working Party 1996 and the update (Northover et al. 2010), there is some variability in potential schedules.
Chemoradiotherapy
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2), started at least 2 hours before the first radiation fraction
- Alternate dosing & schedule (per physician discretion): Fluorouracil (5-FU) 750 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m2)
- Mitomycin (Mutamycin) 12 mg/m2 (maximum dose of 20 mg) IV bolus once on day 1
- Concurrent radiation therapy: 1.8 or 2.25 Gy fractions x 20 or 25 fractions (total dose: 45 Gy), given over 4 to 5 weeks; see Northover et al. 2010 for details, including information about boost radiation therapy
28-day cycle for 2 cycles
Variant #4, 4000/12/50.4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
James et al. 2013 (ACT II) | Phase III (C) | Fluorouracil, Cisplatin, RT | Seems not superior |
Chemoradiotherapy
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
- Mitomycin (Mutamycin) 12 mg/m2 (maximum dose of 20 mg) IV bolus once on day 1
- Concurrent radiation therapy: 1.8 Gy per day x 28 fractions (total dose: 50.4 Gy), given over 5.5 weeks; see paper for details
28-day cycle for 2 cycles
Subsequent treatment
- CF maintenance versus no further treatment
References
- Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, Quivey J, Rotman M, Kerman H, Coia L, Murray K. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996 Sep;14(9):2527-39. link to original article contains verified protocol PubMed
- ACT I: Northover JMA, Arnott SJ, Cunningham D, Gallagher J, Gray R, Hardcastle J, Houghton J, James RD, Lennon TA, Meadows HM, Mossman J, Morgan DAL, Plowman PN, Slevin M; UKCCCR Anal Cancer Trial Working Party; UK Co-ordinating Committee on Cancer Research. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996 Oct 19;348(9034):1049-54. link to original article contains verified protocol PubMed
- Update: Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010 Mar 30;102(7):1123-8. Epub 2010 Mar 16. link to original article contains verified protocol PubMed content property of HemOnc.org
- Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997 May;15(5):2040-9. link to original article contains protocol PubMed
- RTOG 98-11: Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett C. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008 Apr 23;299(16):1914-21. link to original article contains verified protocol PubMed
- Update: Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012 Dec 10;30(35):4344-51. Epub 2012 Nov 13. link to original article link to PMC article PubMed
- ACT II: James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial. Lancet Oncol. 2013 May;14(6):516-24. link to original article contains verified protocol PubMed
Radiation therapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Northover et al. 1996 (ACT I) | Phase III (C) | Fluorouracil, Mitomycin, radiation | Inferior local failure rate |
Inferior to combined modality therapy; included for reference purposes only.
Radiotherapy
References
- ACT I: Northover JMA, Arnott SJ, Cunningham D, Gallagher J, Gray R, Hardcastle J, Houghton J, James RD, Lennon TA, Meadows HM, Mossman J, Morgan DAL, Plowman PN, Slevin M; UKCCCR Anal Cancer Trial Working Party; UK Co-ordinating Committee on Cancer Research. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996 Oct 19;348(9034):1049-54. link to original article contains verified protocol PubMed
- Update: Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010 Mar 30;102(7):1123-8. Epub 2010 Mar 16. link to original article contains verified protocol PubMed content property of HemOnc.org
Metastatic disease, first-line therapy
Cisplatin & Fluorouracil
back to top |
Variant #1, 100/5000 every 4 weeks
Study | Evidence |
---|---|
Faivre et al. 1999 | Pilot, <20 patients reported |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m2)
28-day cycles
Variant #2, 60/4000 every 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sclafani et al. 2017 | Randomized Phase II (C) | Carboplatin & Paclitaxel | Not reported |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycles
References
- Faivre C, Rougier P, Ducreux M, Mitry E, Lusinchi A, Lasser P, Elias D, Eschwege F. [5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer]. Bull Cancer. 1999 Oct;86(10):861-5. link to original article & English summary contains protocol PubMed
- Abstract: Sclafani F et al. [InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease]. Journal of Clinical Oncology. 2015 33:3_suppl, TPS792-TPS792. link to abstract contains protocol clinicaltrials.gov
Carboplatin & Paclitaxel
back to top |
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV on days 1, 8, 15
28-day cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sclafani et al. 2017 | Randomized Phase II (C) | Cisplatin & 5-FU | Not reported |
References
- Abstract: Sclafani F et al. [InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease]. Journal of Clinical Oncology. 2015 33:3_suppl, TPS792-TPS792. link to abstract contains protocol clinicaltrials.gov
mDCF
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mDCF: modified Docetaxel, Cisplatin, Fluorouracil
Regimen
Study | Evidence |
---|---|
Kim et al. 2018 (Epitopes-HPV02) | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 40 mg/m2 IV once on day 1
- Cisplatin (Platinol) 40 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1200 mg/m2/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 2400 mg/m2)
14-day cycle for 8 cycles
References
- Epitopes-HPV02: Kim S, François E, André T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouché O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, De La Fouchardiere C, Smith D, Deberne M, Spehner L, Badet N, Adotevi O, Anota A, Meurisse A, Vernerey D, Taieb J, Vendrely V, Buecher B, Borg C. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018 Aug;19(8):1094-1106. Epub 2018 Jul 2. link to original article PubMed
Metastatic disease, subsequent lines of therapy
Nivolumab monotherapy
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Regimen
Study | Evidence |
---|---|
Morris et al. 2017 (NCI9673) | Phase II |
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
14-day cycles
References
- NCI9673: Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL, Xiao L, Bekaii-Saab T, Vence L, Blando J, Mahvash A, Foo WC, Ohaji C, Pasia M, Bland G, Ohinata A, Rogers J, Mehdizadeh A, Banks K, Lanman R, Wolff RA, Streicher H, Allison J, Sharma P, Eng C. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017 Apr;18(4):446-453. Epub 2017 Feb 18. link to original article link to PMC article PubMed
Pembrolizumab monotherapy
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Regimen
Study | Evidence |
---|---|
Ott et al. 2017 (KEYNOTE-028) | Phase Ib, >20 pts in this subgroup |
Immunotherapy
- Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1
14-day cycle for up to 2 years
References
- KEYNOTE-028: Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E, Simonelli M, Morosky A, Saraf S, Emancipator K, Koshiji M, Bennouna J. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017 May 1;28(5):1036-1041. link to original article link to PMC article contains protocol PubMed