Difference between revisions of "Cervical cancer"

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m (formatting of headers)
(updated & verified regimens)
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−
=Chemotherapy & radiation therapy=
+
=Chemoradiation=
−
==Cisplatin (Platinol) & RT==
+
==Cisplatin (Platinol), XRT, brachytherapy==
−
===Regimen #1 (Rose, et al. 1999 and Rose, et al. 2007)===
+
===Regimen #1, Rose, et al. 1999 & Rose, et al. 2007===
−
*[[Cisplatin (Platinol)]] 40 mg/m2 IV 4 hours before radiation therapy on days 1, 8, 15, 22, 29, 36  
+
Chemoradiation:
−
*Concurrent radiation therapy:
+
*[[Cisplatin (Platinol)]] 40 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
−
**Stage IIB disease: 1.7 Gy per dose x 24 fractions for a total of 40.8 Gy  
+
*Concurrent radiation therapy
−
**Stage III/IVA disease: 1.7 Gy per dose x 30 fractions for a total of 51.0 Gy  
+
**Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
 +
**Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
  
−
'''6-week course of chemotherapy & radiation, then'''
+
'''6-week course'''
  
−
*Intracavitary brachytherapy 1-3 weeks after external beam radiation therapy (XRT):
+
Brachytherapy:
−
**Stage IIB disease: 40 Gy  
+
*Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
−
**Stage III/IVA 30 Gy
+
*Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
−
*See Rose et al, 1999 & 2007 articles for additional details about radiation
+
**Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
  
−
===Regimen #2 (Lanciano, et al. 2005)===
+
'''brachytherapy starts 1-3 weeks after external beam radiation'''
−
*[[Cisplatin (Platinol)]] 40 mg/m2 (maximum weekly dose of 70 mg) IV 4 hours before radiation therapy on days 1, 8, 15, 22, 29, 36
 
−
*Concurrent radiation therapy at 1.8 Gy per dose x 25 fractions for a total of 45 Gy
 
−
*Intracavitary brachytherapy:
 
−
**EITHER high-dose rate (HDR) brachytherapy 30 Gy administered in 5 fractions, starting during week 4
 
−
**OR low-dose rate (LDR) brachytherapy 40 Gy in 1-2 fractions (no start date specified)
 
−
*Parametrial boost, 5.4-9.0 Gy to the involved parametrium after whole pelvis RT is complete
 
  
−
===Regimen #3 (Keys, et al. 1999)===
+
===Regimen #2, Dueñas-González, et al. 2011===
−
*[[Cisplatin (Platinol)]] 40 mg/m2 (maximum weekly dose of 70 mg) IV 4 hours before radiation therapy on days 1, 8, 15, 22, 29, 36
+
Chemoradiation:
−
*Concurrent radiation therapy at 1.8-2.0 Gy per dose over 4.5-5 weeks for a total of 45 Gy
+
*[[Cisplatin (Platinol)]] 40 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36, 1-2 hours before radiation
−
*Intracavitary brachytherapy given that resulted in 30 Gy to the point 2 cm lateral and 2 cm superior to the cervical os) for a cumulative dose of 75 Gy a cumulative dose to the pelvic wall of 55 Gy
+
*Concurrent radiation therapy, 1.8 Gy x 28 fractions given 5 days per week, for an initial dose of 50.4 Gy
 +
 
 +
'''6-week course'''
 +
 
 +
Brachytherapy:
 +
*Brachytherapy with cesium-137, with 30-35 Gy delivered to point A
 +
 
 +
===Regimen #3, Lanciano, et al. 2005===
 +
Chemoradiation:
 +
*[[Cisplatin (Platinol)]] 40 mg/m2 (maximum of 70 mg per dose) IV on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
 +
*Concurrent radiation therapy, 1.8 Gy x 25 fractions, for an initial dose of 40.8 Gy
 +
*Brachytherapy involved:
 +
**EITHER Low-dose rate intracavitary brachytherapy of 40 Gy to point A given in 1-2 fractions
 +
**OR High-dose rate intracavitary brachytherapy of 30 Gy to point A given in 5 fractions, starting week 4 of XRT
 +
*Parametrial boost of 5.4-9 Gy was administered to the involved parametrium after whole pelvic RT was complete
 +
 
 +
===Regimen #4, Keys, et al. 1999===
 +
Chemoradiation:
 +
*[[Cisplatin (Platinol)]] 40 mg/m2 (maximum of 70 mg per dose) IV on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
 +
*Concurrent radiation therapy, 1.8-2 Gy given 5 days per week, for an initial dose of 45 Gy
 +
*After external beam radiation, low-dose brachytherapy was administered, with 30 Gy to point A for a total dose of 75 Gy
  
 
===References===
 
===References===
−
# Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401503 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202166 PubMed]
+
# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
−
# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
+
# Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401503 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202166 PubMed]
−
# Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [http://jco.ascopubs.org/content/23/33/8289.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16230678 PubMed]
+
# Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [http://jco.ascopubs.org/content/23/33/8289.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16230678 PubMed]
−
# Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
+
# Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
 +
# Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [http://jco.ascopubs.org/content/29/13/1678.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21444871 PubMed]
  
−
==Cisplatin (Platinol), Fluorouracil (5-FU), RT==
+
==Cisplatin (Platinol), Fluorouracil (5-FU), XRT==
 
===Regimen===
 
===Regimen===
 +
Chemoradiation:
 
*[[Cisplatin (Platinol)]] 70 mg/m2 IV over 2 hours on day 1
 
*[[Cisplatin (Platinol)]] 70 mg/m2 IV over 2 hours on day 1
−
*[[Fluorouracil (5-FU)]] 1000 mg/m2/day IV over 96-hour continuous infusion on days 1-4
+
*[[Fluorouracil (5-FU)]] 1000 mg/m2/day IV continuous infusion over 96 hours (4000 mg/m2 total dose) on days 1-4
  
 
'''21-day cycles x 4 cycles'''
 
'''21-day cycles x 4 cycles'''
  
−
*Concurrent radiation therapy 1.7 Gy x 29 fractions for a total of 49.3 Gy during cycles 1 & 2
+
Radiation therapy:
−
**Patients with positive high common iliac lymph nodes also received 1.5 Gy x 30 fractions for a total of 45 Gy to the involved area
+
*Concurrent radiation therapy, 1.7 Gy x 29 fractions given 5 days per week, for a total dose of 49.3 Gy
 +
**Patients with positive high common iliac lymph nodes also received 1.5 Gy x 30 fractions given 5 days per week, for a total dose of 45 Gy
 +
 
 +
'''6-week course, started on cycle 1 day 1'''
  
 
===References===
 
===References===
−
# Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [http://jco.ascopubs.org/content/18/8/1606.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10764420 PubMed]
+
# Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [http://jco.ascopubs.org/content/18/8/1606.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10764420 PubMed]
  
−
==Cisplatin (Platinol), Fluorouracil (5-FU), Hydroxyurea (Hydrea), RT==
+
==Cisplatin (Platinol), Fluorouracil (5-FU), Hydroxyurea (Hydrea), XRT, brachytherapy==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on days 1 & 29, 4 hours before radiation therapy
+
Chemoradiation:
−
*[[Fluorouracil (5-FU)]] 1000 mg/m2/day IV over 96-hour continuous infusion on days 1-4 & 29-32
+
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on days 1 & 29
−
*[[Hydroxyurea (Hydrea)]] 2000 mg/m2 PO twice per week, 2 hours before radiation therapy
+
*[[Fluorouracil (5-FU)]] 1000 mg/m2/day IV continuous infusion over 96 hours (4000 mg/m2 total dose) on days 1-4, 29-32
−
*Concurrent radiation therapy:
+
*[[Hydroxyurea (Hydrea)]] 2000 mg/m2 PO two times per week, 2 hours before radiation on weeks 1-6
−
**Stage IIB disease: 1.7 Gy per dose x 24 fractions for a total of 40.8 Gy  
+
*Concurrent radiation therapy
−
**Stage III/IVA disease: 1.7 Gy per dose x 30 fractions for a total of 51.0 Gy  
+
**Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
 +
**Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy
  
−
'''6-week course of chemotherapy & radiation, then'''
+
'''6-week course'''
  
−
*Intracavitary brachytherapy 1-3 weeks after external beam radiation therapy (XRT):
+
Brachytherapy:
−
**Stage IIB disease: 40 Gy  
+
*Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
−
**Stage III/IVA 30 Gy
+
*Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
−
*See Rose et al, 1999 & 2007 articles for additional details about radiation
+
**Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy
 +
 
 +
'''brachytherapy starts 1-3 weeks after external beam radiation'''
  
 
===References===
 
===References===
−
# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
+
# Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [http://www.nejm.org/doi/full/10.1056/NEJM199904153401502 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10202165 PubMed]
−
# Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
+
# Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [http://jco.ascopubs.org/content/25/19/2804.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17502627 PubMed]
 +
 
 +
==Cisplatin (Platinol), Gemcitabine (Gemzar), XRT, brachytherapy==
 +
===Regimen===
 +
Chemoradiation:
 +
*[[Cisplatin (Platinol)]] 40 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36, given first, 1-2 hours before radiation
 +
*[[Gemcitabine (Gemzar)]] 125 mg/m2 IV over 30-60 minutes on days 1, 8, 15, 22, 29, 36, given second, 1-2 hours before radiation
 +
*Concurrent radiation therapy, 1.8 Gy x 28 fractions given 5 days per week, for an initial dose of 50.4 Gy
 +
 
 +
'''6-week course'''
 +
 
 +
Brachytherapy:
 +
*Brachytherapy with cesium-137, with 30-35 Gy delivered to point A
 +
 
 +
Chemotherapy:
 +
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV on days 1 & 8
 +
 
 +
'''21-day cycles x 2 cycles, to start 2 weeks after the end of brachytherapy'''
 +
 
 +
===References===
 +
# Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [http://jco.ascopubs.org/content/29/13/1678.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21444871 PubMed]
  
 
=Neoadjuvant chemotherapy=
 
=Neoadjuvant chemotherapy=
 
==Cisplatin (Platinol) & Paclitaxel (Taxol)==
 
==Cisplatin (Platinol) & Paclitaxel (Taxol)==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 60 mg/m2 IV day 1 (administered second)
+
*[[Cisplatin (Platinol)]] 60 mg/m2 IV over 2 hours on day 1, given second
−
*[[Paclitaxel (Taxol)]] 60 mg/m2 IV over 3 hours day 1 (administered first)
+
*[[Paclitaxel (Taxol)]] 60 mg/m2 IV over 3 hours on day 1, given first
  
 
'''10-day cycles x 3 cycles'''
 
'''10-day cycles x 3 cycles'''
 +
 +
*Clinical response assessed after 3 cycles with pelvic examination and MRI
 +
 +
Supportive medications:
 +
*[[Dexamethasone (Decadron)]] 20 mg PO 12 and 6 hours before paclitaxel
 +
*Cimetidine (Tagamet) 300 mg IV 30 minutes prior to paclitaxel
 +
*Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to paclitaxel
 +
*[[antiemesis|Antiemetics]] before and 3 days after chemotherapy
 +
 +
===References===
 +
# Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. [http://www.sciencedirect.com/science/article/pii/S0090825803006474 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14751139 PubMed]
 +
 +
=Metastatic disease=
 +
==Bevacizumab (Avastin)==
 +
===Regimen===
 +
*[[Bevacizumab (Avastin)]] 15 mg/kg IV on day 1
 +
 +
'''21-day cycles'''
  
 
===References===
 
===References===
−
# Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. [http://www.sciencedirect.com/science/article/pii/S0090825803006474 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14751139 PubMed]
+
# Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. [http://jco.ascopubs.org/content/27/7/1069.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19139430 PubMed]
 +
 
 +
==Carboplatin (Paraplatin)==
 +
===Regimen===
 +
*[[Carboplatin (Paraplatin)]] 400 mg/m2 IV on day 1
 +
 
 +
'''28-day cycles'''
 +
 
 +
===References===
 +
# Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. [http://www.ncbi.nlm.nih.gov/pubmed/2258080 PubMed]
 +
 
 +
==Carboplatin (Paraplatin) & Docetaxel (Taxotere)==
 +
===Regimen===
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 1 hour on day 1, given second
 +
*[[Docetaxel (Taxotere)]] 60 mg/m2 IV over 1 hour on day 1, given first
 +
 
 +
'''21-day cycles'''
 +
 
 +
Supportive medications:
 +
*[[Dexamethasone (Decadron)]]
 +
*Ondansetron or granisetron for [[antiemesis]]
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg daily for patients with grade 4 neutropenia or febrile neutropenia
 +
 
 +
===References===
 +
# Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer. A pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. [http://www.sciencedirect.com/science/article/pii/S0090825804009758 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15721429 PubMed]
 +
 
 +
==Carboplatin (Paraplatin) & Paclitaxel (Taxol)==
 +
===Regimen===
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 1 hour on day 1
 +
*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours on day 1
 +
 
 +
'''21-day cycles x 6-9 cycles'''
 +
 
 +
===References===
 +
# Moore KN, Herzog TJ, Lewin S, Giuntoli RL, Armstrong DK, Rocconi RP, Spannuth WA, Gold MA. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol. 2007 May;105(2):299-303. Epub 2007 Feb 14. [http://www.sciencedirect.com/science/article/pii/S009082580600970X link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17303230 PubMed]
 +
# Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. [http://journals.lww.com/ijgc/pages/articleviewer.aspx?year=2009&issue=05000&article=00049&type=abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19509587 PubMed]
  
−
=Chemotherapy for metastatic disease=
 
 
==Cisplatin (Platinol)==
 
==Cisplatin (Platinol)==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 50 mg/m2 IV day 1  
+
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1
 +
 
 +
'''21-day cycles; if not responding, given for maximum of 6 cycles'''
 +
 
 +
===References===
 +
# Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [http://jco.ascopubs.org/content/22/15/3113.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15284262 PubMed]
 +
# Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [http://jco.ascopubs.org/content/23/21/4626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15911865 PubMed]
 +
 
 +
==Cisplatin (Platinol) & Gemcitabine (Gemzar)==
 +
===Regimen #1, Brewer, et al. 2006===
 +
*[[Cisplatin (Platinol)]] 30 mg/m2 IV on day 1, given first
 +
*[[Gemcitabine (Gemzar)]] 800 mg/m2 IV on days 1 & 8, given second
 +
 
 +
'''28-day cycles'''
 +
 
 +
===Regimen #2, Monk, et al. 2009===
 +
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV on days 1 & 8
  
 
'''21-day cycles'''
 
'''21-day cycles'''
  
 
===References===
 
===References===
−
# Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. [http://jco.ascopubs.org/content/3/8/1079.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/3894589 PubMed]
+
# Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. [http://www.sciencedirect.com/science/article/pii/S0090825805007894 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16271750 PubMed]
 +
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
  
−
==Cisplatin (Platinol) & Gemcitabine (Gemzar)==
+
==Cisplatin (Platinol) & Mitomycin (Mutamycin)==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 50 mg/m2 IV day 1  
+
''Note: The NCCN, Cervical Cancer version 1.2012, lists mitomycin monotherapy as a potential second-line therapy option, and cites the reference below, which describes a two-drug regimen.  No primary reference for the monotherapy regimen could be found.''
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV days 1 & 8
+
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1, given second
 +
*[[Mitomycin (Mutamycin)]] 6 mg/m2 IV push on day 1, given first
  
−
'''21-day cycles x up to 6 cycles'''
+
'''28-day cycles x 9 cycles'''
 +
 
 +
Supportive hydration:
 +
*1 liter NS over 1 hour and furosemide before chemotherapy, and 1 liter NS over 1 hour after cisplatin
 +
*Mannitol IV push prior to cisplatin
  
 
===References===
 
===References===
−
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+
# Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. [http://www.ejcancer.info/article/S0959-8049%2801%2900178-2/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11527687 PubMed]
  
 
==Cisplatin (Platinol) & Paclitaxel (Taxol)==
 
==Cisplatin (Platinol) & Paclitaxel (Taxol)==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 50 mg/m2 IV day 2  
+
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 2
−
*[[Paclitaxel (Taxol)]] 135 mg/m2 IV over 24 hours day 1
+
*[[Paclitaxel (Taxol)]] 135 mg/m2 IV continuous infusion over 24 hours on day 1
  
−
'''21-day cycles x up to 6 cycles'''
+
'''21-day cycles; if not responding, given for maximum of 6 cycles'''
 +
 
 +
Supportive medications (varies depending on reference):
 +
*[[Dexamethasone (Decadron)]], Diphenhydramine (Benadryl), H2 receptor antagonist (such as Cimetidine (Tagamet) or Ranitidine (Zantac)), and prophlactic [[Antiemesis|antiemetics]].
 +
*"Adequate IV hydration and electrolyte replacement"
  
 
===References===
 
===References===
−
# Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [http://jco.ascopubs.org/content/22/15/3113.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15284262 PubMed]
+
# Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [http://jco.ascopubs.org/content/22/15/3113.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15284262 PubMed]
−
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
  
 
==Cisplatin (Platinol) & Topotecan (Hycamtin)==
 
==Cisplatin (Platinol) & Topotecan (Hycamtin)==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 50 mg/m2 IV day 1
+
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1, given after topotecan
−
*[[Topotecan (Hycamtin)]] 0.75 mg/m2 IV over 30 minutes days 1-3
+
*[[Topotecan (Hycamtin)]] 0.75 mg/m2 IV over 30 minutes on days 1-3
  
−
'''21-day cycles x up to 6 cycles'''
+
'''21-day cycles; if not responding, given for maximum of 6 cycles'''
  
 
===References===
 
===References===
−
# Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [http://jco.ascopubs.org/content/23/21/4626.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15911865 PubMed]
+
# Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [http://jco.ascopubs.org/content/23/21/4626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15911865 PubMed]
−
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
  
 
==Cisplatin (Platinol) & Vinorelbine (Navelbine)==
 
==Cisplatin (Platinol) & Vinorelbine (Navelbine)==
 
===Regimen===
 
===Regimen===
−
*[[Cisplatin (Platinol)]] 50 mg/m2 IV day 1
+
*[[Cisplatin (Platinol)]] 50 mg/m2 IV on day 1
−
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV days 1 & 8
+
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV on days 1 & 8
 +
 
 +
'''21-day cycles; if not responding, given for maximum of 6 cycles'''
 +
 
 +
===References===
 +
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
 +
 
 +
==Docetaxel (Taxotere)==
 +
===Regimen #1, Garcia, et al. 2007===
 +
*[[Docetaxel (Taxotere)]] 100 mg/m2 IV over 1 hour on day 1
 +
 
 +
'''21-day cycles'''
 +
 
 +
===Regimen #2, Garcia, et al. 2008===
 +
*[[Docetaxel (Taxotere)]] 36 mg/m2 IV over 1 hour on days 1, 8, 15
 +
 
 +
'''28-day cycles'''
 +
 
 +
Supportive medications:
 +
*[[Dexamethasone (Decadron)]] 8 mg PO the evening before, morning of, and evening of each dose of docetaxel
 +
 
 +
===References===
 +
# Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group Study. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study. Am J Clin Oncol. 2007 Aug;30(4):428-31. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2007&issue=08000&article=00014&type=abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17762444 PubMed]
 +
# Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. [http://www.sciencedirect.com/science/article/pii/S0090825808004526 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18675446 PubMed]
 +
 
 +
==Fluorouracil (5-FU) & Folinic acid (Leucovorin)==
 +
===Regimen #1, Look, et al. 1996 & Look, et al. 1997===
 +
*[[Folinic acid (Leucovorin)]] 200 mg/m2 IV bolus on days 1-5, given first
 +
*[[Fluorouracil (5-FU)]] 370 mg/m2 IV bolus over 5 minutes on days 1-5, given second
 +
 
 +
'''28-day cycles x 2 cycles, then 35-day cycles given until progression of disease or unacceptable toxicity'''
 +
 
 +
===Regimen #2, Look, et al. 1992===
 +
*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV on days 1-5, given first
 +
*[[Fluorouracil (5-FU)]] 425 mg/m2 IV on days 1-5, given second
 +
 
 +
'''28-day cycles x 2 cycles, then 35-day cycles given until progression of disease or unacceptable toxicity'''
 +
 
 +
===References===
 +
# Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. [http://www.ncbi.nlm.nih.gov/pubmed/1449112 PubMed]
 +
# Look KY, Blessing JA, Gallup DG, Lentz SS. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. [http://www.ncbi.nlm.nih.gov/pubmed/8823469 PubMed]
 +
# Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. [http://www.sciencedirect.com/science/article/pii/S0090825897948861 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9441772 PubMed]
 +
 
 +
==Gemcitabine (Gemzar)==
 +
===Regimen===
 +
*[[Gemcitabine (Gemzar)]] 800 mg/m2 IV over 30 minutes on days 1, 8, 15
 +
 
 +
'''28-day cycles'''
 +
 
 +
===References===
 +
# Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic oncology group. Gynecol Oncol. 2000 Feb;76(2):204-7. [http://www.sciencedirect.com/science/article/pii/S0090825899956718 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10637071 PubMed]
 +
# Schilder RJ, Blessing J, Cohn DE. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. [http://www.sciencedirect.com/science/article/pii/S0090825804007735 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15589587 PubMed]
 +
 
 +
==Ifosfamide (Ifex)==
 +
===Regimen===
 +
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV on days 1-5
 +
**Dosage for patients with previous pelvic radiation or other chemotherapy is [[Ifosfamide (Ifex)]] 1200 mg/m2
 +
**Dose of [[Ifosfamide (Ifex)]] could be increased by 300 mg/m2 or decreased by 20% depending on toxicity
 +
*[[Mesna (Mesnex)]] at 20% of ifosfamide dose (for example, 300 mg/m2 for 1500 mg/m2 dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1-5
  
−
'''21-day cycles x up to 6 cycles'''
+
'''21-day cycles'''
  
 
===References===
 
===References===
−
# Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4649.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720909 PubMed]
+
# Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, et al. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. [http://www.ncbi.nlm.nih.gov/pubmed/3802384 PubMed]
 +
# Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. [http://www.ncbi.nlm.nih.gov/pubmed/8456884 PubMed]
 +
# Sutton GP, Blessing JA, DiSaia PJ, McGuire WP. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. [http://www.sciencedirect.com/science/article/pii/S009082588371084X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8482560 PubMed]
  
−
==Carboplatin (Paraplatin) & Docetaxel (Taxotere)==
+
==Irinotecan (Camptosar)==
 
===Regimen===
 
===Regimen===
−
*[[Carboplatin (Paraplatin)]] AUC 6 IV day 1 (administered second)
+
*[[Irinotecan (Camptosar)]] 125 mg/m2 IV over 90 minutes on days 1, 8, 15, 22
−
*[[Docetaxel (Taxotere)]] 60 mg/m2 IV day 1 (administered first)
+
 
 +
'''42-day cycles'''
  
−
'''21-day cycles x up to 6 cycles'''
+
Supportive medications:
 +
*Diphenhydramine (Benadryl) 25-50 mg PO/IV every 6 hours as needed for diarrhea during irinotecan infusion
 +
*Atropine 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion
 +
*Loperamide 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions
  
 
===References===
 
===References===
−
# Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer. A pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. [http://www.sciencedirect.com/science/article/pii/S0090825804009758 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15721429 PubMed]
+
# Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. [http://jco.ascopubs.org/content/15/2/625.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9053486 PubMed]
  
 
==Paclitaxel (Taxol)==
 
==Paclitaxel (Taxol)==
 +
===Regimen #1, Kudelka, et al. 1996 & Kudelka, et al. 1997===
 +
*[[Paclitaxel (Taxol)]] 250 mg/m2 IV over 3 hours on day 1
 +
**Dose of [[Paclitaxel (Taxol)]] could be changed to 275, 225, or 200 mg/m2 depending on toxicity
 +
 +
'''21-day cycles'''
 +
 +
Supportive medications:
 +
*[[Dexamethasone (Decadron)]] 20 mg PO 14 and 7 hours prior to paclitaxel
 +
*Cimetidine (Tagamet) 300 mg IV 60 minutes prior to paclitaxel
 +
*Diphenhydramine (Benadryl) 50 mg IV 60 minutes prior to paclitaxel
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC daily starting on day 2, 24 hours after chemotherapy, given until day 19 or until ANC greater or equal to 10,000
 +
 +
===Regimen #2, McGuire, et al. 1996 & Curtin, et al. 2001===
 +
*[[Paclitaxel (Taxol)]] 170 mg/m2 IV continuous infusion over 24 hours on day 1
 +
**Dosage for patients with previous pelvic radiation was [[Paclitaxel (Taxol)]] 135 mg/m2
 +
**Dose of [[Paclitaxel (Taxol)]] could be changed to 110 or 200 mg/m2 depending on toxicity
 +
 +
'''21-day cycles'''
 +
 +
Supportive medications:
 +
*[[Dexamethasone (Decadron)]] 20 mg PO/IV 14 and 7 hours prior to paclitaxel
 +
*Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to paclitaxel
 +
*Ranitidine (Zantac) 50 mg IV 30 minutes prior to paclitaxel
 +
 +
===References===
 +
# McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. [http://jco.ascopubs.org/content/14/3/792.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8622025 PubMed]
 +
# Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. [http://clincancerres.aacrjournals.org/content/2/8/1285.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9816298 PubMed]
 +
# Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. [http://www.ncbi.nlm.nih.gov/pubmed/9311440 PubMed]
 +
# Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. [http://jco.ascopubs.org/content/19/5/1275.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11230468 PubMed]
 +
 +
==Pemetrexed (Alimta)==
 
===Regimen===
 
===Regimen===
−
*[[Paclitaxel (Taxol)]] 170 mg/m2 (135 mg/m2 for patients who previously received pelvic radiation) IV over 24-hour continuous infusion day 1
+
*[[Pemetrexed (Alimta)]] 900 mg/m2 IV over 10 minutes on day 1
−
**Subsequent dose modifications of Paclitaxel (Taxol) to 110-200 mg/m2 per dose based on adverse effects
+
 
 +
'''21-day cycles'''
  
−
'''21-day cycles x up to 6 cycles'''
+
Supportive medications:
 +
*Folic acid 350-600 mcg PO daily, starting 7 days before pemetrexed, to continue throughout therapy
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once 7 days before pemetrexed (then 1000 mcg to be given every 9 weeks thereafter)
 +
*[[Dexamethasone (Decadron)]] 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta
 +
*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed
  
 
===References===
 
===References===
−
# McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. [http://jco.ascopubs.org/content/14/3/792.abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8622025 PubMed]
+
# Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. [http://www.sciencedirect.com/science/article/pii/S0090825808002035 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18455781 PubMed]
−
# Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. [http://jco.ascopubs.org/content/19/5/1275.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11230468 PubMed]
 
  
 
==Topotecan (Hycamtin)==
 
==Topotecan (Hycamtin)==
−
===Regimen===
+
===Regimen #1, Bookman, et al. 2000===
−
*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV on days 1-5
+
*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV over 30 minutes on days 1-5
 +
 
 +
'''21-day cycles'''
 +
 
 +
===Regimen #2, Muderspach, et al. 2001===
 +
*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV over 30 minutes on days 1-5
  
−
'''21 to 28-day cycles'''
+
'''28-day cycles'''
  
 
===References===
 
===References===
−
# Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. [http://www.sciencedirect.com/science/article/pii/S0090825800958074 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10831357 PubMed]
+
# Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. [http://www.sciencedirect.com/science/article/pii/S0090825800958074 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10831357 PubMed]
−
# Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol. 2001 May;81(2):213-5. [http://www.sciencedirect.com/science/article/pii/S0090825800960244 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11354055 PubMed]
+
# Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol. 2001 May;81(2):213-5. [http://www.sciencedirect.com/science/article/pii/S0090825800960244 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11354055 PubMed]
  
 
==Vinorelbine (Navelbine)==
 
==Vinorelbine (Navelbine)==
−
===Regimen===
+
===Regimen #1, Muggia, et al. 2004 & Muggia, et al. 2005===
−
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV day 1
+
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV on days 1 & 8
 +
 
 +
'''21-day cycles'''
 +
 
 +
===Regimen #2, Morris, et al. 1998===
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV on day 1
  
 
'''7-day cycles'''
 
'''7-day cycles'''
  
 
===References===
 
===References===
−
# Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. [http://jco.ascopubs.org/content/16/3/1094.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9508195 PubMed]
+
# Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. [http://jco.ascopubs.org/content/16/3/1094.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9508195 PubMed]
 +
# Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group study. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. [http://www.sciencedirect.com/science/article/pii/S0090825803007704 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14766259 PubMed]
 +
# Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group Study. Gynecol Oncol. 2005 Jan;96(1):108-11. [http://www.sciencedirect.com/science/article/pii/S0090825804007747 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15589588 PubMed]

Revision as of 22:25, 7 May 2012

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Chemoradiation

Cisplatin (Platinol), XRT, brachytherapy

Regimen #1, Rose, et al. 1999 & Rose, et al. 2007

Chemoradiation:

  • Cisplatin (Platinol) 40 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
  • Concurrent radiation therapy
    • Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
    • Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy

6-week course

Brachytherapy:

  • Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
  • Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
    • Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy

brachytherapy starts 1-3 weeks after external beam radiation

Regimen #2, Dueñas-González, et al. 2011

Chemoradiation:

  • Cisplatin (Platinol) 40 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36, 1-2 hours before radiation
  • Concurrent radiation therapy, 1.8 Gy x 28 fractions given 5 days per week, for an initial dose of 50.4 Gy

6-week course

Brachytherapy:

  • Brachytherapy with cesium-137, with 30-35 Gy delivered to point A

Regimen #3, Lanciano, et al. 2005

Chemoradiation:

  • Cisplatin (Platinol) 40 mg/m2 (maximum of 70 mg per dose) IV on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
  • Concurrent radiation therapy, 1.8 Gy x 25 fractions, for an initial dose of 40.8 Gy
  • Brachytherapy involved:
    • EITHER Low-dose rate intracavitary brachytherapy of 40 Gy to point A given in 1-2 fractions
    • OR High-dose rate intracavitary brachytherapy of 30 Gy to point A given in 5 fractions, starting week 4 of XRT
  • Parametrial boost of 5.4-9 Gy was administered to the involved parametrium after whole pelvic RT was complete

Regimen #4, Keys, et al. 1999

Chemoradiation:

  • Cisplatin (Platinol) 40 mg/m2 (maximum of 70 mg per dose) IV on days 1, 8, 15, 22, 29, 36, 4 hours before radiation
  • Concurrent radiation therapy, 1.8-2 Gy given 5 days per week, for an initial dose of 45 Gy
  • After external beam radiation, low-dose brachytherapy was administered, with 30 Gy to point A for a total dose of 75 Gy

References

  1. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains verified protocol PubMed
  2. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. link to original article contains verified protocol PubMed
  3. Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains verified protocol PubMed
  4. Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed
  5. Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains verified protocol PubMed

Cisplatin (Platinol), Fluorouracil (5-FU), XRT

Regimen

Chemoradiation:

21-day cycles x 4 cycles

Radiation therapy:

  • Concurrent radiation therapy, 1.7 Gy x 29 fractions given 5 days per week, for a total dose of 49.3 Gy
    • Patients with positive high common iliac lymph nodes also received 1.5 Gy x 30 fractions given 5 days per week, for a total dose of 45 Gy

6-week course, started on cycle 1 day 1

References

  1. Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. link to original article contains verified protocol PubMed

Cisplatin (Platinol), Fluorouracil (5-FU), Hydroxyurea (Hydrea), XRT, brachytherapy

Regimen

Chemoradiation:

  • Cisplatin (Platinol) 50 mg/m2 IV on days 1 & 29
  • Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours (4000 mg/m2 total dose) on days 1-4, 29-32
  • Hydroxyurea (Hydrea) 2000 mg/m2 PO two times per week, 2 hours before radiation on weeks 1-6
  • Concurrent radiation therapy
    • Stage IIB patients received 1.7 Gy x 24 fractions, for an initial dose of 40.8 Gy
    • Stage III or IVA disease received 1.7 Gy x 30 fractions, for an initial dose of 51 Gy

6-week course

Brachytherapy:

  • Stage IIB patients received 40 Gy by intracavitary brachytherapy, for a total dose of 80.8 Gy to point A
  • Stage III or IVA disease received 30 Gy by intracavitary brachytherapy, for a total dose of 81 Gy to point A
    • Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 61.2 Gy

brachytherapy starts 1-3 weeks after external beam radiation

References

  1. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains verified protocol PubMed
  2. Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed

Cisplatin (Platinol), Gemcitabine (Gemzar), XRT, brachytherapy

Regimen

Chemoradiation:

  • Cisplatin (Platinol) 40 mg/m2 IV over 60 minutes on days 1, 8, 15, 22, 29, 36, given first, 1-2 hours before radiation
  • Gemcitabine (Gemzar) 125 mg/m2 IV over 30-60 minutes on days 1, 8, 15, 22, 29, 36, given second, 1-2 hours before radiation
  • Concurrent radiation therapy, 1.8 Gy x 28 fractions given 5 days per week, for an initial dose of 50.4 Gy

6-week course

Brachytherapy:

  • Brachytherapy with cesium-137, with 30-35 Gy delivered to point A

Chemotherapy:

21-day cycles x 2 cycles, to start 2 weeks after the end of brachytherapy

References

  1. Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains verified protocol PubMed

Neoadjuvant chemotherapy

Cisplatin (Platinol) & Paclitaxel (Taxol)

Regimen

10-day cycles x 3 cycles

  • Clinical response assessed after 3 cycles with pelvic examination and MRI

Supportive medications:

  • Dexamethasone (Decadron) 20 mg PO 12 and 6 hours before paclitaxel
  • Cimetidine (Tagamet) 300 mg IV 30 minutes prior to paclitaxel
  • Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to paclitaxel
  • Antiemetics before and 3 days after chemotherapy

References

  1. Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. link to original article contains verified protocol PubMed

Metastatic disease

Bevacizumab (Avastin)

Regimen

21-day cycles

References

  1. Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. link to original article contains verified protocol PubMed

Carboplatin (Paraplatin)

Regimen

28-day cycles

References

  1. Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. PubMed

Carboplatin (Paraplatin) & Docetaxel (Taxotere)

Regimen

21-day cycles

Supportive medications:

References

  1. Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer. A pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. link to original article contains verified protocol PubMed

Carboplatin (Paraplatin) & Paclitaxel (Taxol)

Regimen

21-day cycles x 6-9 cycles

References

  1. Moore KN, Herzog TJ, Lewin S, Giuntoli RL, Armstrong DK, Rocconi RP, Spannuth WA, Gold MA. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol. 2007 May;105(2):299-303. Epub 2007 Feb 14. link to original article PubMed
  2. Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. link to original article contains protocol PubMed

Cisplatin (Platinol)

Regimen

21-day cycles; if not responding, given for maximum of 6 cycles

References

  1. Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. link to original article contains verified protocol PubMed
  2. Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. link to original article contains verified protocol PubMed

Cisplatin (Platinol) & Gemcitabine (Gemzar)

Regimen #1, Brewer, et al. 2006

28-day cycles

Regimen #2, Monk, et al. 2009

21-day cycles

References

  1. Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. link to original article contains verified protocol PubMed
  2. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains verified protocol PubMed

Cisplatin (Platinol) & Mitomycin (Mutamycin)

Regimen

Note: The NCCN, Cervical Cancer version 1.2012, lists mitomycin monotherapy as a potential second-line therapy option, and cites the reference below, which describes a two-drug regimen. No primary reference for the monotherapy regimen could be found.

28-day cycles x 9 cycles

Supportive hydration:

  • 1 liter NS over 1 hour and furosemide before chemotherapy, and 1 liter NS over 1 hour after cisplatin
  • Mannitol IV push prior to cisplatin

References

  1. Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. link to original article contains verified protocol PubMed

Cisplatin (Platinol) & Paclitaxel (Taxol)

Regimen

21-day cycles; if not responding, given for maximum of 6 cycles

Supportive medications (varies depending on reference):

  • Dexamethasone (Decadron), Diphenhydramine (Benadryl), H2 receptor antagonist (such as Cimetidine (Tagamet) or Ranitidine (Zantac)), and prophlactic antiemetics.
  • "Adequate IV hydration and electrolyte replacement"

References

  1. Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. link to original article contains verified protocol PubMed
  2. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains verified protocol PubMed

Cisplatin (Platinol) & Topotecan (Hycamtin)

Regimen

21-day cycles; if not responding, given for maximum of 6 cycles

References

  1. Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. link to original article contains verified protocol PubMed
  2. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains verified protocol PubMed

Cisplatin (Platinol) & Vinorelbine (Navelbine)

Regimen

21-day cycles; if not responding, given for maximum of 6 cycles

References

  1. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains verified protocol PubMed

Docetaxel (Taxotere)

Regimen #1, Garcia, et al. 2007

21-day cycles

Regimen #2, Garcia, et al. 2008

28-day cycles

Supportive medications:

References

  1. Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group Study. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study. Am J Clin Oncol. 2007 Aug;30(4):428-31. link to original article contains protocol PubMed
  2. Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. link to original article contains verified protocol PubMed

Fluorouracil (5-FU) & Folinic acid (Leucovorin)

Regimen #1, Look, et al. 1996 & Look, et al. 1997

28-day cycles x 2 cycles, then 35-day cycles given until progression of disease or unacceptable toxicity

Regimen #2, Look, et al. 1992

28-day cycles x 2 cycles, then 35-day cycles given until progression of disease or unacceptable toxicity

References

  1. Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. PubMed
  2. Look KY, Blessing JA, Gallup DG, Lentz SS. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. PubMed
  3. Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. link to original article contains verified protocol PubMed

Gemcitabine (Gemzar)

Regimen

28-day cycles

References

  1. Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic oncology group. Gynecol Oncol. 2000 Feb;76(2):204-7. link to original article contains verified protocol PubMed
  2. Schilder RJ, Blessing J, Cohn DE. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. link to original article contains verified protocol PubMed

Ifosfamide (Ifex)

Regimen

  • Ifosfamide (Ifex) 1500 mg/m2 IV on days 1-5
    • Dosage for patients with previous pelvic radiation or other chemotherapy is Ifosfamide (Ifex) 1200 mg/m2
    • Dose of Ifosfamide (Ifex) could be increased by 300 mg/m2 or decreased by 20% depending on toxicity
  • Mesna (Mesnex) at 20% of ifosfamide dose (for example, 300 mg/m2 for 1500 mg/m2 dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1-5

21-day cycles

References

  1. Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, et al. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. PubMed
  2. Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. PubMed
  3. Sutton GP, Blessing JA, DiSaia PJ, McGuire WP. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. link to original article contains verified protocol PubMed

Irinotecan (Camptosar)

Regimen

42-day cycles

Supportive medications:

  • Diphenhydramine (Benadryl) 25-50 mg PO/IV every 6 hours as needed for diarrhea during irinotecan infusion
  • Atropine 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion
  • Loperamide 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions

References

  1. Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. link to original article contains verified protocol PubMed

Paclitaxel (Taxol)

Regimen #1, Kudelka, et al. 1996 & Kudelka, et al. 1997

21-day cycles

Supportive medications:

  • Dexamethasone (Decadron) 20 mg PO 14 and 7 hours prior to paclitaxel
  • Cimetidine (Tagamet) 300 mg IV 60 minutes prior to paclitaxel
  • Diphenhydramine (Benadryl) 50 mg IV 60 minutes prior to paclitaxel
  • Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day 2, 24 hours after chemotherapy, given until day 19 or until ANC greater or equal to 10,000

Regimen #2, McGuire, et al. 1996 & Curtin, et al. 2001

21-day cycles

Supportive medications:

  • Dexamethasone (Decadron) 20 mg PO/IV 14 and 7 hours prior to paclitaxel
  • Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to paclitaxel
  • Ranitidine (Zantac) 50 mg IV 30 minutes prior to paclitaxel

References

  1. McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. link to original article contains verified protocol PubMed
  2. Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. link to original article contains verified protocol PubMed
  3. Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. PubMed
  4. Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. link to original article contains verified protocol PubMed

Pemetrexed (Alimta)

Regimen

21-day cycles

Supportive medications:

  • Folic acid 350-600 mcg PO daily, starting 7 days before pemetrexed, to continue throughout therapy
  • Cyanocobalamin (Vitamin B12) 1000 mcg IM once 7 days before pemetrexed (then 1000 mcg to be given every 9 weeks thereafter)
  • Dexamethasone (Decadron) 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta
  • No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed

References

  1. Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. link to original article contains verified protocol PubMed

Topotecan (Hycamtin)

Regimen #1, Bookman, et al. 2000

21-day cycles

Regimen #2, Muderspach, et al. 2001

28-day cycles

References

  1. Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. link to original article contains verified protocol PubMed
  2. Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol. 2001 May;81(2):213-5. link to original article contains verified protocol PubMed

Vinorelbine (Navelbine)

Regimen #1, Muggia, et al. 2004 & Muggia, et al. 2005

21-day cycles

Regimen #2, Morris, et al. 1998

7-day cycles

References

  1. Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. link to original article contains verified protocol PubMed
  2. Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group study. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. link to original article contains verified protocol PubMed
  3. Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group Study. Gynecol Oncol. 2005 Jan;96(1):108-11. link to original article contains verified protocol PubMed
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