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Carcinoma of unknown primary may also be referred to as carcinoma of unknown primary site, cancer/carcinoma of unknown primary (CUP), occult primary, or unknown primary carcinoma.

15 regimens on this page 16 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

2020: Maghami et al. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline PubMed

ESMO

2023: Krämer et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2015: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2011: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Pavlidis et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up PubMed
- 2007: Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Briasoulis et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) PubMed
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) PubMed

NCCN

NCCN Guidelines - Occult Primary
- 2014: Ettinger et al. Occult Primary, Version 3.2014 PubMed
- 2011: Ettinger et al. NCCN Clinical Practice Guidelines Occult primary. PubMed
- 2005: Ettinger et al. Occult primary cancer clinical practice guidelines. PubMed

All lines of therapy

BEP

BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PEB: Platinol (Cisplatin), Etoposide, Bleomycin

Regimen

Study	Dates of enrollment	Evidence
Hainsworth et al 1992	1978-02 to 1989-12	Phase 2

Chemotherapy

Bleomycin (Blenoxane) 30 units IV once per day on days 1, 8, 15
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5
Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 5

21-day cycles

References

Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. link to original article contains dosing details in manuscript PubMed

Carboplatin & Docetaxel

Regimen variant #1

Study	Dates of enrollment	Evidence
Pentheroudakis et al. 2008	2000-01 to NR	Phase 2

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second
Docetaxel (Taxotere) 75 mg/m² IV over 30 minutes once on day 1, given first

Supportive therapy

Dexamethasone (Decadron) 8 mg PO twice per day on day -1, then 16 mg IV once on day 1, prior to chemotherapy
Ondansetron (Zofran) 8 mg IV once on day 1, prior to chemotherapy
Ranitidine (Zantac) 100 mg IV once on day 1, prior to chemotherapy
Dimetindene (Fenistil) 0.1 mg/kg (route unclear) prior to chemotherapy

21-day cycle for up to 8 cycles

Regimen variant #2

Study	Dates of enrollment	Evidence
Greco et al. 2000 Study A	1996-11 to 1997-08	Phase 2

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 20 minutes once on day 1, given second
Docetaxel (Taxotere) 65 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2
One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) 32 mg IV once on day 1; 15 minutes prior to chemotherapy
- Granisetron 10 mcg/kg IV once on day 1; 15 minutes prior to chemotherapy

21-day cycle for 4 to 8 cycles

References

Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. link to original article contains dosing details in manuscript PubMed
Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. link to original article contains dosing details in manuscript PubMed

Carboplatin & Gemcitabine (GCb) & Paclitaxel

GCP: Gemcitabine, Carboplatin, Paclitaxel

Regimen

Study	Dates of enrollment	Evidence
Greco et al. 2002	1998-12 to 2000-08	Phase 2

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Carboplatin (Paraplatin) AUC 5 IV over 20 to 30 minutes once on day 1
Paclitaxel (Taxol) 200 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Corticosteroids IV once on day 1; 30 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycles

References

Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. link to original article contains dosing details in manuscript PubMed

Carboplatin & Paclitaxel (CP)

Regimen

Study	Dates of enrollment	Evidence
Briasoulis et al. 2000	1996-02 to 1999-02	Phase 2
Hayashi et al. 2019	2008-10 to 2015-02	Phase 2

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given first
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given second

Supportive therapy

per Briasoulis 2000 study

Methylprednisolone (Solumedrol) 32 mg PO for three doses, 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin
Dexamethasone (Decadron) 16 mg IV once on day 1, at least 10 minutes prior to chemotherapy
One of the following antihistamines:
- Diphenhydramine (Benadryl) 50 mg IV once on day 1, at least 10 minutes prior to chemotherapy
- Dimetindene (Fenistil) 0.1 mg/kg IV once on day 1, at least 10 minutes prior to chemotherapy
Ranitidine (Zantac) 100 mg IV once on day 1, at least 10 minutes prior to chemotherapy
Ondansetron (Zofran) 8 mg IV once on day 1, after the above premedications
Suggested: Filgrastim (Neupogen) 300 mcg SC once per day on days 5 to 12

21-day cycle for 6 to 8 cycles

References

Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N; Hellenic Cooperative Oncology Group. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. link to original article contains dosing details in manuscript PubMed
Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoe T, Mukai H, Matsubara N, Minami H, Toyoda M, Onozawa Y, Ono A, Fujita Y, Sakai K, Koh Y, Takeuchi A, Ohashi Y, Nishio K, Nakagawa K. Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site. J Clin Oncol. 2019 Mar 1;37(7):570-579. Epub 2019 Jan 17. link to original article contains dosing details in manuscript PubMed

Cisplatin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gross-Goupil et al. 2012 (GEFCAPI 02)	2003-2007	Randomized Phase 2 (C)	Cisplatin & Gemcitabine	Did not meet primary endpoint of OS

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

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1

21-day cycles

References

GEFCAPI 02: Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. link to original article contains dosing details in manuscript PubMed NCT00126269

Cisplatin & Docetaxel (DC)

Regimen

Study	Dates of enrollment	Evidence
Greco et al. 2000 Study B	1997-09 to 1998-10	Phase 2

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 60 minutes once on day 1
Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2
- Suggested: 20 mg IV once on day 1; 15 minutes prior to cisplatin
2 liters of normal saline with chemotherapy
One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) 32 mg IV once on day 1; 15 minutes prior to cisplatin
- Granisetron 10 mcg/kg IV once on day 1; 15 minutes prior to cisplatin
Ondansetron (Zofran) 8 mg PO three times per day on days 2 to 6

21-day cycle for up to 8 cycles

References

Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. link to original article contains dosing details in manuscript PubMed

Cisplatin & Gemcitabine (GC)

GC: Gemcitabine & Cisplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Culine et al. 2003 (GEFCAPI 01)	1999-2000	Randomized Phase 2 (E-switch-ic)	Cisplatin & Irinotecan	Not reported
Gross-Goupil et al. 2012 (GEFCAPI 02)	2003-2007	Randomized Phase 2 (E-esc)	Cisplatin	Did not meet primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1250 mg/m² IV once per day on days 1 & 8

21-day cycles

References

GEFCAPI 01: Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
GEFCAPI 02: Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. link to original article contains dosing details in manuscript PubMed NCT00126269

Cisplatin & Irinotecan (IC)

IC: Irinotecan & Cisplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Culine et al. 2003 (GEFCAPI 01)	1999-2000	Randomized Phase 2 (E-switch-ic)	Cisplatin & Gemcitabine	Not reported

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Irinotecan (Camptosar) 150 mg/m² IV once on day 1

21-day cycles

References

GEFCAPI 01: Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. link to original article contains dosing details in manuscript PubMed

DCF

DCF: Docetaxel, Cisplatin, Fluorouracil

Regimen

Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1
Cisplatin (Platinol) 75 mg/m² IV once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m²)

Supportive therapy

1 liter normal saline before and after cisplatin +/- mannitol, potassium chloride, magnesium sulfate
Dexamethasone (Decadron) 8 mg PO once per day the day before, the day of, and day after chemotherapy
Ciprofloxacin (Cipro) 1000 mg PO (reference did not specify, but assume 500 mg twice per day) on days 5 to 15

21-day cycle for 3 cycles

References

None that we are aware of

Docetaxel & Gemcitabine

Regimen

Study	Dates of enrollment	Evidence
Pouessel et al. 2004	2000-12 to 2003-04	Phase 2

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 8
Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8

Supportive therapy

Corticosteroids PO the day before, the day of, and day after docetaxel

21-day cycle for up to 6 cycles

References

Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. link to original article contains dosing details in manuscript PubMed

Erlotinib & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence
Hainsworth et al. 2007a	2004-04 to 2005-07	Phase 2

Targeted therapy

Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28
Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
- Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later

28-day cycles

References

Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. link to original article contains dosing details in manuscript PubMed

Gemcitabine & Irinotecan

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hainsworth et al. 2010 (SCRI UNKPRI 12)	2003-2008	Phase 3 (E-switch-ic)	PCE	Did not meet primary endpoint of OS24

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Irinotecan (Camptosar) 100 mg/m² IV once per day on days 1 & 8

21-day cycle for up to 6 cycles

References

SCRI UNKPRI 12: Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. link to original article PubMed NCT00193596

Nivolumab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Tanizaki et al. 2021	2018-02-19 to 2019-08-09	Phase 2 (RT)

Note: This was the trial supporting PMDA approval for this indication.

Immunotherapy

Nivolumab (Opdivo) 240 mg IV once on day 1

14-day cycle for up to 52 cycles (2 years)

References

Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H. Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022 Feb;33(2):216-226. Epub 2021 Nov 26. link to original article PubMed UMIN000030649

PCE

PCE: Paclitaxel, Carboplatin, Etoposide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Greco et al. 2000a	1995-1996	Phase 2
Hainsworth et al. 2010 (SCRI UNKPRI 12)	2003-2008	Phase 3 (E-switch-ic)	Gemcitabine & Irinotecan	Did not meet primary endpoint of OS24

Chemotherapy

Paclitaxel (Taxol) 200 mg/m² IV over 60 minutes once on day 1
Carboplatin (Paraplatin) AUC 6 IV over 20 to 30 minutes once on day 1
Etoposide (Vepesid) as follows:
- Days 1, 3, 5, 7, 9: 50 mg PO once per day
- Days 2, 4, 6, 8, 10: 100 mg PO once per day

Supportive therapy

Dexamethasone (Decadron) 20 mg PO for two doses, 12 hours and 4 hours prior to paclitaxel
Dexamethasone (Decadron) 20 mg IV once on day 1; 30 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycle for 4 to 8 cycles

References

Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalman LA, Schreeder MT, Hainsworth JD. Carcinoma of unknown primary site. Cancer. 2000 Dec 15;89(12):2655-60. link to original article contains dosing details in manuscript PubMed
SCRI UNKPRI 12: Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. link to original article PubMed NCT00193596

PCF

PCF: Paclitaxel, Cisplatin, Fluorouracil

Regimen

Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 2
Fluorouracil (5-FU) 500 mg/m²/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 2500 mg/m²)

21-day cycle for 3 cycles

References

None that we are aware of

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+[[#top|Back to Top]]
+</div>
 Carcinoma of unknown primary may also be referred to as carcinoma of unknown primary site, cancer/carcinoma of unknown primary (CUP), occult primary, or unknown primary carcinoma.
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+=Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
+==[https://www.asco.org/ ASCO]==
+*'''2020:''' Maghami et al. [https://doi.org/10.1200/jco.20.00275 Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline] [https://pubmed.ncbi.nlm.nih.gov/32324430/ PubMed]
-=Guidelines=
+==[https://www.esmo.org/ ESMO]==
-==[http://www.esmo.org/ ESMO]==
+*'''2023:''' Krämer et al. [https://doi.org/10.1016/j.annonc.2022.11.013 Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/36563965 PubMed]
-*'''2015:''' Fizazi et al. [https://doi.org/10.1093/annonc/mdv305 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+**'''2015:''' Fizazi et al. [https://doi.org/10.1093/annonc/mdv305 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/26314775 PubMed]
-===Older===
+**'''2011:''' Fizazi et al. [https://doi.org/10.1093/annonc/mdr389 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/21908507 PubMed]
-*'''2011:''' Fizazi et al. [https://doi.org/10.1093/annonc/mdr389 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+**'''2010:''' Pavlidis et al. [https://doi.org/10.1093/annonc/mdq193 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/20555087 PubMed]
-*'''2010:''' Pavlidis et al. [https://doi.org/10.1093/annonc/mdq193 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+**'''2009:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdp159 Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/19454441 PubMed]
-*'''2009:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdp159 Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up]
+**'''2008:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdn104 Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/18456742 PubMed]
-*'''2008:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdn104 Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up]
+**'''2007:''' [https://doi.org/10.1093/annonc/mdm049 Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/17491060 PubMed]
-*'''2007:''' [https://doi.org/10.1093/annonc/mdm049 Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up]
+**'''2005:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdi804 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)] [https://www.ncbi.nlm.nih.gov/pubmed/15888766 PubMed]
-*'''2005:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdi804 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)]
+**'''2001:''' [https://doi.org/10.1023/a:1017409423484 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)] [https://www.ncbi.nlm.nih.gov/pubmed/11583184 PubMed]
-*'''2001:''' [https://doi.org/10.1023/a:1017409423484 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)]
-==[https://www.nccn.org/ NCCN]==
+==NCCN==
-*[https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf NCCN Guidelines - Occult Primary (Cancer of Unknown Primary (CUP)]
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1451 NCCN Guidelines - Occult Primary]
+**'''2014:''' Ettinger et al. [https://doi.org/10.6004/jnccn.2014.0093 Occult Primary, Version 3.2014] [https://pubmed.ncbi.nlm.nih.gov/24994917/ PubMed]
+**'''2011:''' Ettinger et al. [https://doi.org/10.6004/Jnccn.2011.0117 NCCN Clinical Practice Guidelines Occult primary.] [https://pubmed.ncbi.nlm.nih.gov/22157556/ PubMed]
+**'''2005:''' Ettinger et al. Occult primary cancer clinical practice guidelines. [https://pubmed.ncbi.nlm.nih.gov/19817031/ PubMed]
 =All lines of therapy=
 ==BEP {{#subobject:cc3566|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 BEP: '''<u>B</u>'''leomycin, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 <br>PEB: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>B</u>'''leomycin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:953c7d|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1200/jco.1992.10.6.912 Hainsworth et al 1992]
-|style="background-color:#91cf61"|Phase II
+|1978-02 to 1989-12
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Bleomycin (Blenoxane)]] 30 units IV once per day on days 1, 8, 15
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 '''21-day cycles'''
+</div></div>
 ===References===
-# Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. [https://doi.org/10.1200/jco.1992.10.6.912 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/1375284 PubMed]
+# Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. [https://doi.org/10.1200/jco.1992.10.6.912 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1375284/ PubMed]
 ==Carboplatin & Docetaxel {{#subobject:44b3f6|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen variant #1 {{#subobject:88482c|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.tandfonline.com/doi/full/10.1080/02841860701843043 Pentheroudakis et al. 2008]
+|[https://doi.org/10.1080/02841860701843043 Pentheroudakis et al. 2008]
-|style="background-color:#91cf61"|Phase II
+|2000-01 to NR
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given second'''
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1, '''given first'''
+====Supportive therapy====
-====Supportive medications====
 *[[Dexamethasone (Decadron)]] 8 mg PO twice per day on day -1, then 16 mg IV once on day 1, '''prior to chemotherapy'''
 *[[Ondansetron (Zofran)]] 8 mg IV once on day 1, '''prior to chemotherapy'''
 *[[Ranitidine (Zantac)]] 100 mg IV once on day 1, '''prior to chemotherapy'''
-*[[Dimethindene maleate (Fenestil)]] 0.1 mg/kg (route unclear) prior to chemotherapy
+*[[Dimetindene (Fenistil)]] 0.1 mg/kg (route unclear) prior to chemotherapy
 '''21-day cycle for up to 8 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:a56594|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1023/a:1008369812295 Greco et al. 2000]
+|[https://doi.org/10.1023/a:1008369812295 Greco et al. 2000 Study A]
-|style="background-color:#91cf61"|Phase II
+|1996-11 to 1997-08
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 6 IV over 20 minutes once on day 1, '''given second'''
 *[[Docetaxel (Taxotere)]] 65 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
-====Supportive medications====
 *[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2
 *One of the following serotonin 5-HT3 antagonists:
 **[[Ondansetron (Zofran)]] 32 mg IV once on day 1; 15 minutes prior to chemotherapy
 **[[Granisetron]] 10 mcg/kg IV once on day 1; 15 minutes prior to chemotherapy
 '''21-day cycle for 4 to 8 cycles'''
+</div></div>
+===References===
+# Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. [https://doi.org/10.1023/a:1008369812295 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10761758/ PubMed]
+# Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. [https://doi.org/10.1080/02841860701843043 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18607872/ PubMed]
+==Carboplatin & Gemcitabine (GCb) & Paclitaxel {{#subobject:4d259f|Regimen=1}}==
+GCP: '''<u>G</u>'''emcitabine, '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:96f90f|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1200/jco.2002.20.6.1651 Greco et al. 2002]
+|1998-12 to 2000-08
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 20 to 30 minutes once on day 1
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Supportive therapy====
+*[[:Category:Steroids|Corticosteroids]] IV once on day 1; 30 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+'''21-day cycles'''
+</div></div>
 ===References===
-# Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. [https://doi.org/10.1023/a:1008369812295 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10761758 PubMed]
+# Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. [https://doi.org/10.1200/jco.2002.20.6.1651 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11896116/ PubMed]
-# Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. [https://www.tandfonline.com/doi/full/10.1080/02841860701843043 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/18607872 PubMed]
 ==Carboplatin & Paclitaxel (CP) {{#subobject:910bdc|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:a386ae|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1200/jco.2000.18.17.3101 Briasoulis et al. 2000]
-|style="background-color:#91cf61"|Phase II
+|1996-02 to 1999-02
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1200/jco.18.00771 Hayashi et al. 2019]
+|2008-10 to 2015-02
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1, '''given first'''
 *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
+====Supportive therapy====
-====Supportive medications====
+per Briasoulis 2000 study
 *[[Methylprednisolone (Solumedrol)]] 32 mg PO for three doses, 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin
 *[[Dexamethasone (Decadron)]] 16 mg IV once on day 1, at least 10 minutes prior to chemotherapy
 *One of the following antihistamines:
 **[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1, at least 10 minutes prior to chemotherapy
-**[[Dimethindene maleate (Fenestil)]] 0.1 mg/kg IV once on day 1, at least 10 minutes prior to chemotherapy
+**[[Dimetindene (Fenistil)]] 0.1 mg/kg IV once on day 1, at least 10 minutes prior to chemotherapy
 *[[Ranitidine (Zantac)]] 100 mg IV once on day 1, at least 10 minutes prior to chemotherapy
 *[[Ondansetron (Zofran)]] 8 mg IV once on day 1, after the above premedications
 *Suggested: [[Filgrastim (Neupogen)]] 300 mcg SC once per day on days 5 to 12
 '''21-day cycle for 6 to 8 cycles'''
+</div></div>
 ===References===
-# Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N; Hellenic Cooperative Oncology Group. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. [https://doi.org/10.1200/jco.2000.18.17.3101 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10963638 PubMed]
+# Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N; Hellenic Cooperative Oncology Group. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. [https://doi.org/10.1200/jco.2000.18.17.3101 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10963638/ PubMed]
+# Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoe T, Mukai H, Matsubara N, Minami H, Toyoda M, Onozawa Y, Ono A, Fujita Y, Sakai K, Koh Y, Takeuchi A, Ohashi Y, Nishio K, Nakagawa K. Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site. J Clin Oncol. 2019 Mar 1;37(7):570-579. Epub 2019 Jan 17. [https://doi.org/10.1200/jco.18.00771 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30653423/ PubMed]
 ==Cisplatin monotherapy {{#subobject:21015c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:a5832e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!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://www.ejcancer.com/article/S0959-8049(12)00018-4/abstract Gross-Goupil et al. 2012 (GEFCAPI 02)]
+|[https://doi.org/10.1016/j.ejca.2012.01.011 Gross-Goupil et al. 2012 (GEFCAPI 02)]
 |2003-2007
-|style="background-color:#1a9851"|Randomized Phase II (C)
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
 |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |}
-''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-# '''GEFCAPI 02:''' Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [https://www.ejcancer.com/article/S0959-8049(12)00018-4/abstract link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22317952 PubMed] NCT00126269
+# '''GEFCAPI 02:''' Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [https://doi.org/10.1016/j.ejca.2012.01.011 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22317952/ PubMed] [https://clinicaltrials.gov/study/NCT00126269 NCT00126269]
 ==Cisplatin & Docetaxel (DC) {{#subobject:27937b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:61bedc|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1023/a:1008369812295 Greco et al. 2000]
+|[https://doi.org/10.1023/a:1008369812295 Greco et al. 2000 Study B]
-|style="background-color:#91cf61"|Phase II
+|1997-09 to 1998-10
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Supportive therapy====
-====Supportive medications====
 *[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2
-**Suggested: 20 mg IV once on day 1; 15 minutes prior to [[Cisplatin (Platinol)]]
+**Suggested: 20 mg IV once on day 1; 15 minutes prior to cisplatin
 *2 liters of normal saline with chemotherapy
 *One of the following serotonin 5-HT3 antagonists:
-**[[Ondansetron (Zofran)]] 32 mg IV once on day 1; 15 minutes prior to [[Cisplatin (Platinol)]]
+**[[Ondansetron (Zofran)]] 32 mg IV once on day 1; 15 minutes prior to cisplatin
-**[[Granisetron]] 10 mcg/kg IV once on day 1; 15 minutes prior to [[Cisplatin (Platinol)]]
+**[[Granisetron]] 10 mcg/kg IV once on day 1; 15 minutes prior to cisplatin
 *[[Ondansetron (Zofran)]] 8 mg PO three times per day on days 2 to 6
 '''21-day cycle for up to 8 cycles'''
+</div></div>
 ===References===
-# Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. [https://doi.org/10.1023/a:1008369812295 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10761758 PubMed]
+# Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. [https://doi.org/10.1023/a:1008369812295 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10761758/ PubMed]
 ==Cisplatin & Gemcitabine (GC) {{#subobject:a36533|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:2506f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 212: / Line 240: @@
 |[https://doi.org/10.1200/jco.2003.12.104 Culine et al. 2003 (GEFCAPI 01)]
 |1999-2000
-|style="background-color:#1a9851"|Randomized Phase II (E-switch-ic)
+|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
 |[[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 |style="background-color:#d3d3d3"|Not reported
 |-
-|[https://www.ejcancer.com/article/S0959-8049(12)00018-4/abstract Gross-Goupil et al. 2012 (GEFCAPI 02)]
+|[https://doi.org/10.1016/j.ejca.2012.01.011 Gross-Goupil et al. 2012 (GEFCAPI 02)]
 |2003-2007
-|style="background-color:#1a9851"|Randomized Phase II (E-esc)
+|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 |[[#Cisplatin_monotherapy|Cisplatin]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 *[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycles'''
+</div></div>
 ===References===
-# '''GEFCAPI 01:''' Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [https://doi.org/10.1200/jco.2003.12.104 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12972523 PubMed] content property of [http://hemonc.org HemOnc.org]
+# '''GEFCAPI 01:''' Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [https://doi.org/10.1200/jco.2003.12.104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12972523/ PubMed] content property of [https://hemonc.org HemOnc.org]
-# '''GEFCAPI 02:''' Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [https://www.ejcancer.com/article/S0959-8049(12)00018-4/abstract link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22317952 PubMed] NCT00126269
+# '''GEFCAPI 02:''' Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [https://doi.org/10.1016/j.ejca.2012.01.011 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22317952/ PubMed] [https://clinicaltrials.gov/study/NCT00126269 NCT00126269]
 ==Cisplatin & Irinotecan (IC) {{#subobject:a7a736|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 IC: '''<u>I</u>'''rinotecan & '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3940e6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 249: / Line 273: @@
 |[https://doi.org/10.1200/jco.2003.12.104 Culine et al. 2003 (GEFCAPI 01)]
 |1999-2000
-|style="background-color:#1a9851"|Randomized Phase II (E-switch-ic)
+|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
 |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]]
 |style="background-color:#d3d3d3"|Not reported
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 *[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-# '''GEFCAPI 01:''' Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [https://doi.org/10.1200/jco.2003.12.104 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12972523 PubMed]
+# '''GEFCAPI 01:''' Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [https://doi.org/10.1200/jco.2003.12.104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12972523/ PubMed]
 ==DCF {{#subobject:3f05e4|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:2ae092|Variant=1}}===
 ''Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 *[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m<sup>2</sup>)
+====Supportive therapy====
-====Supportive medications====
+*1 liter normal saline before and after cisplatin +/- mannitol, potassium chloride, magnesium sulfate
-*1 liter normal saline before and after [[Cisplatin (Platinol)]] +/- mannitol, potassium chloride, magnesium sulfate
 *[[Dexamethasone (Decadron)]] 8 mg PO once per day the day before, the day of, and day after chemotherapy
 *[[Ciprofloxacin (Cipro)]] 1000 mg PO (reference did not specify, but assume 500 mg twice per day) on days 5 to 15
 '''21-day cycle for 3 cycles'''
+</div></div>
 ===References===
 # None that we are aware of
 ==Docetaxel & Gemcitabine {{#subobject:d61b91|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:a67a4e|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.20100/full Pouessel et al. 2004]
+|[https://doi.org/10.1002/cncr.20100 Pouessel et al. 2004]
-|style="background-color:#91cf61"|Phase II
+|2000-12 to 2003-04
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
+====Supportive therapy====
-====Supportive medications====
+*[[:Category:Steroids|Corticosteroids]] PO the day before, the day of, and day after docetaxel
-*[[:Category:Steroids|Corticosteroids]] PO the day before, the day of, and day after [[Docetaxel (Taxotere)]]
 '''21-day cycle for up to 6 cycles'''
+</div></div>
 ===References===
-# Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.20100/full link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/15022294 PubMed]
+# Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. [https://doi.org/10.1002/cncr.20100 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15022294/ PubMed]
 ==Erlotinib & Bevacizumab {{#subobject:742957|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:e0f611|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1200/jco.2006.09.3047 Hainsworth et al. 2007a]
-|style="background-color:#91cf61"|Phase II
+|2004-04 to 2005-07
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Erlotinib (Tarceva)]] 150 mg PO on days 1 to 28, 1 hour before or 2 hours after meals
+*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28
 *[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 **Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later
 '''28-day cycles'''
+</div></div>
 ===References===
-# Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. [https://doi.org/10.1200/jco.2006.09.3047 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17470864 PubMed]
+# Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. [https://doi.org/10.1200/jco.2006.09.3047 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17470864/ PubMed]
-==GCP {{#subobject:4d259f|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-GCP: '''<u>G</u>'''emcitabine, '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel
-===Regimen {{#subobject:96f90f|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.2002.20.6.1651 Greco et al. 2002]
-|style="background-color:#91cf61"|Phase II
-|-
-|}
-====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 20 to 30 minutes once on day 1
-*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-====Supportive medications====
-*[[:Category:Steroids|Corticosteroids]] IV once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
-*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
-'''21-day cycles'''
-===References===
-# Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. [https://doi.org/10.1200/jco.2002.20.6.1651 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/11896116 PubMed]
 ==Gemcitabine & Irinotecan {{#subobject:3f6501|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:6a2c02|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!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]]
 |-
-|[http://journals.lww.com/journalppo/pages/articleviewer.aspx?year=2010&issue=02000&article=00013&type=abstract Hainsworth et al. 2010]
+|[https://doi.org/10.1097/ppo.0b013e3181c6aa89 Hainsworth et al. 2010 (SCRI UNKPRI 12)]
 |2003-2008
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 |[[#PCE|PCE]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS24
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+# '''SCRI UNKPRI 12:''' Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. [https://doi.org/10.1097/ppo.0b013e3181c6aa89 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20164695/ PubMed] [https://clinicaltrials.gov/study/NCT00193596 NCT00193596]
+==Nivolumab monotherapy {{#subobject:3fni01|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ni2c02|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.annonc.2021.11.009 Tanizaki et al. 2021]
+|2018-02-19 to 2019-08-09
+| style="background-color:#91cf61" |Phase 2 (RT)
+|-
+|}
+''Note: This was the trial supporting PMDA approval for this indication.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Nivolumab (Opdivo)]] 240 mg IV once on day 1
+'''14-day cycle for up to 52 cycles (2 years)'''
+</div></div>
 ===References===
-# Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. [http://journals.lww.com/journalppo/pages/articleviewer.aspx?year=2010&issue=02000&article=00013&type=abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/20164695 PubMed]
+#Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H. Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022 Feb;33(2):216-226. Epub 2021 Nov 26. [https://doi.org/10.1016/j.annonc.2021.11.009 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34843940/ PubMed] UMIN000030649
 ==PCE {{#subobject:87de5a|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 PCE: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:886058|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!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://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2820001215%2989:12%3C2655::AID-CNCR19%3E3.0.CO;2-9/full Greco et al. 2000a]
+|[https://doi.org/10.1002/1097-0142%2820001215%2989:12%3C2655::AID-CNCR19%3E3.0.CO;2-9 Greco et al. 2000a]
 |1995-1996
-|style="background-color:#91cf61"|Phase II
+|style="background-color:#91cf61"|Phase 2
 |style="background-color:#d3d3d3"|
 |style="background-color:#d3d3d3"|
 |-
-|[http://journals.lww.com/journalppo/pages/articleviewer.aspx?year=2010&issue=02000&article=00013&type=abstract Hainsworth et al. 2010]
+|[https://doi.org/10.1097/ppo.0b013e3181c6aa89 Hainsworth et al. 2010 (SCRI UNKPRI 12)]
 |2003-2008
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 |[[#Gemcitabine_.26_Irinotecan|Gemcitabine & Irinotecan]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS24
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
@@ Line 427: / Line 428: @@
 **Days 1, 3, 5, 7, 9: 50 mg PO once per day
 **Days 2, 4, 6, 8, 10: 100 mg PO once per day
+====Supportive therapy====
-====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg PO for two doses, 12 hours and 4 hours prior to paclitaxel
-*[[Dexamethasone (Decadron)]] 20 mg PO for two doses, 12 hours and 4 hours prior to [[Paclitaxel (Taxol)]]
+*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1; 30 minutes prior to paclitaxel
-*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
-*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
 '''21-day cycle for 4 to 8 cycles'''
+</div></div>
 ===References===
-# Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalman LA, Schreeder MT, Hainsworth JD. Carcinoma of unknown primary site. Cancer. 2000 Dec 15;89(12):2655-60. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2820001215%2989:12%3C2655::AID-CNCR19%3E3.0.CO;2-9/full link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/11135228 PubMed]
+# Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalman LA, Schreeder MT, Hainsworth JD. Carcinoma of unknown primary site. Cancer. 2000 Dec 15;89(12):2655-60. [https://doi.org/10.1002/1097-0142%2820001215%2989:12%3C2655::AID-CNCR19%3E3.0.CO;2-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11135228/ PubMed]
-# Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. [http://journals.lww.com/journalppo/pages/articleviewer.aspx?year=2010&issue=02000&article=00013&type=abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/20164695 PubMed]
+# '''SCRI UNKPRI 12:''' Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. [https://doi.org/10.1097/ppo.0b013e3181c6aa89 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20164695/ PubMed] [https://clinicaltrials.gov/study/NCT00193596 NCT00193596]
 ==PCF {{#subobject:71face|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 PCF: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c82ab5|Variant=1}}===
 ''Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
 *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 2500 mg/m<sup>2</sup>)
 '''21-day cycle for 3 cycles'''
+</div></div>
 ===References===
 # None that we are aware of
 [[Category:Carcinoma of unknown primary regimens]]
 [[Category:Site-agnostic regimens]]
 [[Category:Malignant solid neoplasm]]

Difference between revisions of "Carcinoma of unknown primary"

Latest revision as of 11:25, 27 June 2024

Guidelines

ASCO

ESMO

NCCN

All lines of therapy

BEP

Regimen

Chemotherapy

References

Carboplatin & Docetaxel

Regimen variant #1

Chemotherapy

Supportive therapy

Regimen variant #2

Chemotherapy

Supportive therapy

References

Carboplatin & Gemcitabine (GCb) & Paclitaxel

Regimen

Chemotherapy

Supportive therapy

References

Carboplatin & Paclitaxel (CP)

Regimen

Chemotherapy

Supportive therapy

References

Cisplatin monotherapy

Regimen

Chemotherapy

References

Cisplatin & Docetaxel (DC)

Regimen

Chemotherapy

Supportive therapy

References

Cisplatin & Gemcitabine (GC)

Regimen

Chemotherapy

References

Cisplatin & Irinotecan (IC)

Regimen

Chemotherapy

References

DCF

Regimen

Chemotherapy

Supportive therapy

References

Docetaxel & Gemcitabine

Regimen

Chemotherapy

Supportive therapy

References

Erlotinib & Bevacizumab

Regimen

Targeted therapy

References

Gemcitabine & Irinotecan

Regimen

Chemotherapy

References

Nivolumab monotherapy

Regimen

Immunotherapy

References

PCE

Regimen

Chemotherapy

Supportive therapy

References

PCF

Regimen

Chemotherapy

References

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