Revision as of 11:27, 13 May 2024

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main urothelial carcinoma page for current regimens.

9 regimens on this page 10 variants on this page

Neoadjuvant chemotherapy

Atezolizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Powles et al. 2019 (ABACUS)	2016-2018	Phase 2

Immunotherapy

Atezolizumab 1200 mg IV over 60 minutes once on day 1

21-day cycle for 2 cycles

Subsequent treatment

Radical cystectomy to be performed 4 to 8 weeks after completion of chemotherapy

References

ABACUS: Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. Epub 2019 Nov 4. link to original article PubMed NCT02662309

Locally advanced or metastatic disease, first-line, platinum-ineligible

Atezolizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Balar et al. 2016 (IMvigor210 untreated)	2014-2015	Phase 2 (RT)	ORR: 23% (95% CI 16-31)

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

21-day cycles

References

IMvigor210 untreated: Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Durán I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thåström A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. Epub 2016 Dec 8. link to original article contains dosing details in abstract link to PMC article PubMed NCT02951767

Locally advanced or metastatic disease, first-line, platinum-eligible

Atezolizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Galsky et al. 2020 (IMvigor130)	2016-2018	Phase 3 (E-switch-ooc)	1a. GCb 1b. GC	Did not meet co-primary endpoint of OS
Galsky et al. 2020 (IMvigor130)	2016-2018	Phase 3 (E-switch-ooc)	2a. GCb & Atezolizumab 2b. GC & Atezolizumab	Not reported

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

21-day cycles

References

IMvigor130: Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. link to original article contains dosing details in manuscript PubMed NCT02807636
1. Update: Bamias A, Davis ID, Galsky MD, Arranz JÁ, Kikuchi E, Grande E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, Panni S, Gumus M, Özgüroğlu M, Mariathasan S, Poloz Y, Bene-Tchaleu F, Lee C, Bernhard S, De Santis M. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):46-61. Epub 2023 Dec 12. link to original article PubMed

Carboplatin & Gemcitabine (GCb) & Atezolizumab

GCb & Atezolizumab: Gemcitabine, Carboplatin, Atezolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Galsky et al. 2020 (IMvigor130)	2016-2018	Phase 3 (E-RT-esc)	1. Atezolizumab	Not reported
Galsky et al. 2020 (IMvigor130)	2016-2018	Phase 3 (E-RT-esc)	2a. GCb 2b. GC	Might have superior OS¹ (co-primary endpoint) Median OS: 16.1 vs 13.4 mo (HR 0.85, 95% CI 0.73-1.00) Seems to have superior PFS (co-primary endpoint) Median PFS: 8.2 vs 6.3 mo (sHR 0.82, 95% CI 0.70-0.96)

¹Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.

Chemotherapy

Carboplatin (Paraplatin) AUC 4.5 IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

21-day cycles

References

IMvigor130: Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. link to original article contains dosing details in manuscript PubMed NCT02807636
1. Update: Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. link to original article PubMed

CISCA

CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sternberg et al. 1977	1976-1977	Non-randomized, fewer than 20 pts
Logothetis et al. 1990	1985-1989	Phase 3 (E-switch-ic)	MVAC	Inferior OS

Note: ORR for this arm of Logothetis et al. 1990 was 46% (95% CI 32-62) versus 65% (95% CI 52-77) in the control arm.

Chemotherapy

Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 2
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 2

Supportive therapy

Forced mannitol diuresis with cisplatin

21-day cycle for up to 6 cycles

References

Sternberg JJ, Bracken RB, Handel PB, Johnson DE. Combination chemotherapy (CISCA) for advanced urinary tract carcinoma: a preliminary report. JAMA. 1977 Nov 21;238(21):2282-7. link to original article PubMed
Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. link to original article contains dosing details in manuscript PubMed

Cisplatin monotherapy

Regimen variant #1, 70 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Soloway et al. 1983	1978-NR	Randomized (C)	Cisplatin & Cyclophosphamide	Did not meet primary endpoint of ORR
Khandekar et al. 1985	1978-1981	Randomized (C)	CAD	Might have inferior ORR
Troner et al. 1987	NR	Phase 3 (C)	CAD	Did not meet endpoint of ORR
Loehrer et al. 1992 (ECOG E5886)	1984-1989	Phase 3 (C)	MVAC	Inferior OS

Note: To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV once on day 1

28-day cycle for up to 6 cycles

Regimen variant #2, 80 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hillcoat et al. 1989	1982-1986	Phase 3 (C)	Cisplatin & Methotrexate	Did not meet efficacy endpoints

Note: To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1

28-day cycles

References

Soloway MS, Einstein A, Corder MP, Bonney W, Prout GR Jr, Coombs J; National Bladder Cancer Collaborative Group A. A comparison of cisplatin and the combination of cisplatin and cyclophosphamide in advanced urothelial cancer: a National Bladder Cancer Collaborative Group A study. Cancer. 1983 Sep 1;52(5):767-72. link to original article PubMed
Khandekar JD, Elson PJ, DeWys WD, Slayton RE, Harris DT. Comparative activity and toxicity of cis-diamminedichloroplatinum (DDP) and a combination of doxorubicin, cyclophosphamide, and DDP in disseminated transitional cell carcinomas of the urinary tract. J Clin Oncol. 1985 Apr;3(4):539-45. link to original article PubMed
Troner M, Birch R, Omura GA, Williams S; Southeastern Cancer Study Group. Phase III comparison of cisplatin alone versus cisplatin, doxorubicin and cyclophosphamide in the treatment of bladder (urothelial) cancer: a Southeastern Cancer Study Group trial. J Urol. 1987 Apr;137(4):660-2. link to original article PubMed
Hillcoat BL, Raghavan D, Matthews J, Kefford R, Yuen K, Woods R, Olver I, Bishop J, Pearson B, Coorey G, Levi J, Abbott RL, Aroney R, Gill PG, McLennan R. A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract. J Clin Oncol. 1989 Jun;7(6):706-9. link to original article contains dosing details in abstract PubMed
ECOG E5886: Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA, Blumenstein B, Trump D. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992 Jul;10(7):1066-73. Erratum in: J Clin Oncol 1993 Feb;11(2):384. link to original article contains dosing details in manuscript PubMed
1. Update: Saxman SB, Propert KJ, Einhorn LH, Crawford ED, Tannock I, Raghavan D, Loehrer PJ Sr, Trump D. Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1997 Jul;15(7):2564-9. link to original article PubMed

Cisplatin & Gemcitabine (GC) & Atezolizumab

GC & Atezolizumab: Gemcitabine, Cisplatin, Atezolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Galsky et al. 2020 (IMvigor130)	2016-2018	Phase 3 (E-RT-esc)	1. Atezolizumab	Not reported
Galsky et al. 2020 (IMvigor130)	2016-2018	Phase 3 (E-RT-esc)	2a. GCb 2b. GC	Might have superior OS¹ (co-primary endpoint) Median OS: 16.1 vs 13.4 mo (HR 0.85, 95% CI 0.73-1.00) Seems to have superior PFS (co-primary endpoint) Median PFS: 8.2 vs 6.3 mo (sHR 0.82, 95% CI 0.70-0.96)

¹Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

21-day cycles

References

IMvigor130: Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. link to original article contains dosing details in manuscript PubMed NCT02807636
1. Update: Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. link to original article PubMed

Durvalumab & Tremelimumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Powles et al. 2020 (DANUBE)	2015-2017	Phase 3 (E-switch-ooc)	1a. GCb 1b. GC	Might have superior OS (co-primary endpoint) Median OS: 15.1 vs 12.1 mo (HR 0.85, 95% CI 0.72-1.02)
Powles et al. 2020 (DANUBE)	2015-2017	Phase 3 (E-switch-ooc)	2. Durvalumab	Not reported

Immunotherapy

Durvalumab (Imfinzi) 1500 mg IV once on day 1
Tremelimumab (Imjudo) as follows:
- Cycles 1 to 4: 75 mg IV once on day 1

28-day cycles

References

DANUBE: Powles T, van der Heijden MS, Castellano D, Galsky MD, Loriot Y, Petrylak DP, Ogawa O, Park SH, Lee JL, De Giorgi U, Bögemann M, Bamias A, Eigl BJ, Gurney H, Mukherjee SD, Fradet Y, Skoneczna I, Tsiatas M, Novikov A, Suárez C, Fay AP, Duran I, Necchi A, Wildsmith S, He P, Angra N, Gupta AK, Levin W, Bellmunt J; DANUBE study investigators. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1574-1588. Epub 2020 Sep 21. link to original article contains dosing details in abstract PubMed NCT02516241

Metastatic disease, platinum-refractory

Atezolizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Powles et al. 2014 (PCD4989g)	2013-2014	Phase 1
Rosenberg et al. 2016 (IMvigor210 previously treated)	2014	Phase 2 (RT)		ORR: 15% (95% CI 11-20)
Powles et al. 2017 (IMvigor211)	2015-01-13 to 2016-02-15	Phase 3 (E-switch-ooc)	1a. Docetaxel 1b. Paclitaxel 1c. Vinflunine	Did not meet primary endpoint of OS

Note: this regimen did not meet its primary endpoint in phase 3; here for historical reference only.

Biomarker eligibility criteria

Patients are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering at least 5% of the tumor area), as determined by an FDA-approved test Patients are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

21-day cycles

References

PCD4989g: Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62. link to original article PubMed NCT01375842
IMvigor210 previously treated: Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. Epub 2016 Mar 4. link to original article link to PMC article contains dosing details in abstract PubMed NCT02108652
IMvigor211: Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, Oudard S, Retz MM, Castellano D, Bamias A, Fléchon A, Gravis G, Hussain S, Takano T, Leng N, Kadel EE 3rd, Banchereau R, Hegde PS, Mariathasan S, Cui N, Shen X, Derleth CL, Green MC, Ravaud A. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018 Feb 24;391(10122):748-757. Epub 2017 Dec 18. link to original article contains dosing details in abstract PubMed NCT02302807

Durvalumab monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Massard et al. 2016 (Study 1108)	2014-2015	Phase 1/2 (RT)	ORR: 31% (95% CI 18 to 47)

Note: this regimen was intended for patients "who had progressed on, been ineligible for, or refused any number of prior therapies".

Immunotherapy

Durvalumab (Imfinzi) 10 mg/kg IV over 60 minutes once on day 1

14-day cycle for up to 26 cycles (1 year). Patients could receive another 12 months of treatment if they experienced disease progression, had not received other anticancer treatment, and did not meet criteria for discontinuation.

References

Study 1108: Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O'Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016 Sep 10;34(26):3119-25. Epub 2016 Jun 6. link to original article contains dosing details in abstract link to PMC article PubMed NCT01693562
1. Update: Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. Epub 2017 Sep 14. link to original article link to PMC article PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Urothelial carcinoma|main urothelial carcinoma page]] for current regimens.
+The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Urothelial carcinoma|main urothelial carcinoma page]] for current regimens.
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 10: / Line 10: @@
 |}
 {{TOC limit|limit=3}}
-=Nonmuscle invasive bladder cancer=
-==Intravesicular Doxorubicin monotherapy {{#subobject:8034b6|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:49ccdb|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://doi.org/10.1016/s0022-5347(17)40002-4 Martínez-Piñeiro et al. 1990]
-| rowspan="2" |1980-1988
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Urothelial_carcinoma#Bacillus_Calmette-Guérin_.28BCG.29_monotherapy|BCG]]
-| style="background-color:#d73027" |Inferior RFS
-|-
-|2. [[Urothelial_carcinoma#Intravesicular_Thiotepa_monotherapy|Thiotepa]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://doi.org/10.1056/NEJM199110243251703 Lamm et al. 1991 (SWOG 8216)]
-|1983-1985
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Urothelial_carcinoma#Bacillus_Calmette-Guérin_.28BCG.29_monotherapy|BCG]]
-| style="background-color:#fc8d59" |Seems to have inferior DFS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 50 mg intravesicularly once on day 1
-'''7-day cycle for 5 cycles, then 30-day cycle for 11 cycles (approximately 1 year)'''
-</div></div>
-===References===
-#Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guérin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [https://doi.org/10.1016/s0022-5347(17)40002-4 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/2106041/ PubMed]
-#'''SWOG 8216:''' Lamm DL, Blumenstein BA, Crawford ED, Montie JE, Scardino P, Grossman HB, Stanisic TH, Smith JA Jr, Sullivan J, Sarosdy MF, Crissman JD, Coltman CA. A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med. 1991 Oct 24;325(17):1205-9. [https://doi.org/10.1056/NEJM199110243251703 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1922207/ PubMed]
-==Intravesicular Thiotepa monotherapy {{#subobject:5b9d6c|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:97d2e7|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-| rowspan="2" |[https://doi.org/10.1016/s0022-5347(17)40002-4 Martínez-Piñeiro et al. 1990]
-| rowspan="2" |1980-1988
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Urothelial_carcinoma#Bacillus_Calmette-Guérin_.28BCG.29_monotherapy|BCG]]
-| style="background-color:#d73027" |Inferior RFS
-|-
-|2. [[#Intravesicular_Doxorubicin_monotherapy|Doxorubicin]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Thiotepa (Thioplex)]] 50 mg intravesicularly x 15 treatments
-</div></div>
-===References===
-#Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guérin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [https://doi.org/10.1016/s0022-5347(17)40002-4 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/2106041/ PubMed]
 =Neoadjuvant chemotherapy=
 ==Atezolizumab monotherapy {{#subobject:3cb963|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:7ae9e3|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 95: / Line 34: @@
 </div></div>
 ===References===
-#'''ABACUS:''' Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov 4. [https://doi.org/10.1038/s41591-019-0628-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31686036/ PubMed] [https://clinicaltrials.gov/study/NCT02662309 NCT02662309]
+#'''ABACUS:''' Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. Epub 2019 Nov 4. [https://doi.org/10.1038/s41591-019-0628-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31686036/ PubMed] [https://clinicaltrials.gov/study/NCT02662309 NCT02662309]
 =Locally advanced or metastatic disease, first-line, platinum-ineligible=
 ==Atezolizumab monotherapy {{#subobject:1d9e29|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:764948|Variant=1}}===
 {| class="wikitable sortable" style="width: 80%; text-align:center;"
@@ Line 107: / Line 47: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568632/ Balar et al. 2016 (IMvigor210 untreated)]
-{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-355-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 |-
-|}
+|} -->
 |2014-2015
 | style="background-color:#91cf61" |Phase 2 (RT)
@@ Line 125: / Line 65: @@
 =Locally advanced or metastatic disease, first-line, platinum-eligible=
 ==Atezolizumab monotherapy {{#subobject:1d9e29|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:764948|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 138: / Line 78: @@
 | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 |1a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>1b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoint of OS
 |-
 |2a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Atezolizumab|GCb & Atezolizumab]]<br>2b. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Atezolizumab|GC & Atezolizumab]]
@@ Line 151: / Line 91: @@
 ===References===
 #'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636]
+##'''Update:''' Bamias A, Davis ID, Galsky MD, Arranz JÁ, Kikuchi E, Grande E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, Panni S, Gumus M, Özgüroğlu M, Mariathasan S, Poloz Y, Bene-Tchaleu F, Lee C, Bernhard S, De Santis M. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):46-61. Epub 2023 Dec 12. [https://doi.org/10.1016/S1470-2045(23)00539-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38101431/ PubMed]
 ==Carboplatin & Gemcitabine (GCb) & Atezolizumab {{#subobject:8tqccz|Regimen=1}}==
 GCb & Atezolizumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''ar'''<u>b</u>'''oplatin, Atezolizumab
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:8q1jx8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 169: / Line 111: @@
 |-
 |2a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>2b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]
-| style="background-color:#91cf60" |Seems to have superior OS (co-primary endpoint)<br>Median OS: 16 vs 13.4 mo<br>(HR 0.83, 95% CI 0.69-1.00)
+| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 16.1 vs 13.4 mo<br>(HR 0.85, 95% CI 0.73-1.00)<br><br>Seems to have superior PFS (co-primary endpoint)<br>Median PFS: 8.2 vs 6.3 mo<br>(sHR 0.82, 95% CI 0.70-0.96)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
@@ Line 182: / Line 125: @@
 ===References===
 #'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636]
+##'''Update:''' Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. [https://doi.org/10.1016/s1470-2045(23)00540-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38101433/ PubMed]
+==CISCA {{#subobject:b60f2a|Regimen=1}}==
+CISCA: '''<u>CIS</u>'''platin, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:2d0b5e|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://jamanetwork.com/journals/jama/article-abstract/356753 Sternberg et al. 1977]
+|1976-1977
+| style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/jco.1990.8.6.1050 Logothetis et al. 1990]
+|1985-1989
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#MVAC_2|MVAC]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''Note: ORR for this arm of Logothetis et al. 1990 was 46% (95% CI 32-62) versus 65% (95% CI 52-77) in the control arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]] 650 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 2
+====Supportive therapy====
+*Forced mannitol diuresis with cisplatin
+'''21-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+#Sternberg JJ, Bracken RB, Handel PB, Johnson DE. Combination chemotherapy (CISCA) for advanced urinary tract carcinoma: a preliminary report. JAMA. 1977 Nov 21;238(21):2282-7. [https://jamanetwork.com/journals/jama/article-abstract/356753 link to original article] [https://pubmed.ncbi.nlm.nih.gov/578848/ PubMed]
+#Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. [https://doi.org/10.1200/jco.1990.8.6.1050 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2189954/ PubMed]
 ==Cisplatin monotherapy {{#subobject:1af7a9|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen variant #1, 70 mg/m<sup>2</sup> {{#subobject:71bd05|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 223: / Line 204: @@
 '''28-day cycle for up to 6 cycles'''
 </div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:8gbd05|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 255: / Line 236: @@
 ==Cisplatin & Gemcitabine (GC) & Atezolizumab {{#subobject:8gajcz|Regimen=1}}==
 GC & Atezolizumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin, Atezolizumab
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:80ihjx8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 271: / Line 252: @@
 |-
 |2a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>2b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]
-| style="background-color:#91cf60" |Seems to have superior OS (co-primary endpoint)<br>Median OS: 16 vs 13.4 mo<br>(HR 0.83, 95% CI 0.69-1.00)
+| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 16.1 vs 13.4 mo<br>(HR 0.85, 95% CI 0.73-1.00)<br><br>Seems to have superior PFS (co-primary endpoint)<br>Median PFS: 8.2 vs 6.3 mo<br>(sHR 0.82, 95% CI 0.70-0.96)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
@@ Line 284: / Line 266: @@
 ===References===
 #'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636]
+##'''Update:''' Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. [https://doi.org/10.1016/s1470-2045(23)00540-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38101433/ PubMed]
 ==Durvalumab & Tremelimumab {{#subobject:5uckl3|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:639ea8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 317: / Line 300: @@
 =Metastatic disease, platinum-refractory=
 ==Atezolizumab monotherapy {{#subobject:451e68|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:feb2e2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 333: / Line 316: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480242/ Rosenberg et al. 2016 (IMvigor210 previously treated)]
-{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-273-1 <span style="color:white;">ESMO-MCBS (1)</span>]'''
 |-
-|}
+|} -->
 |2014
 | style="background-color:#91cf61" |Phase 2 (RT)
@@ Line 367: / Line 350: @@
 ==Durvalumab monotherapy {{#subobject:7ae7fb|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:b2af36|Variant=1}}===
 {| class="wikitable sortable" style="width: 80%; text-align:center;"

Difference between revisions of "Urothelial carcinoma - historical"

Revision as of 11:27, 13 May 2024

Neoadjuvant chemotherapy

Atezolizumab monotherapy

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Immunotherapy

Subsequent treatment

References

Locally advanced or metastatic disease, first-line, platinum-ineligible

Atezolizumab monotherapy

Regimen

Immunotherapy

References

Locally advanced or metastatic disease, first-line, platinum-eligible

Atezolizumab monotherapy

Regimen

Immunotherapy

References

Carboplatin & Gemcitabine (GCb) & Atezolizumab

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Chemotherapy

Immunotherapy

References

CISCA

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Supportive therapy

References

Cisplatin monotherapy

Regimen variant #1, 70 mg/m2

Chemotherapy

Regimen variant #2, 80 mg/m2

Chemotherapy

References

Cisplatin & Gemcitabine (GC) & Atezolizumab

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Chemotherapy

Immunotherapy

References

Durvalumab & Tremelimumab

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Immunotherapy

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Regimen variant #1, 70 mg/m²

Regimen variant #2, 80 mg/m²