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COMMENTARY
Year : 2020  |  Volume : 152  |  Issue : 5  |  Page : 442-443

Nab-paclitaxel - Third-line chemotherapy in advanced gallbladder cancer


1 Department of Medical Oncology, Army Hospital, Research & Referral, New Delhi 110 010, India
2 Department of Medical Oncology, Apollo Proton Cancer Centre, Chennai 600 028, Tamil Nadu, India

Date of Submission31-Dec-2019
Date of Web Publication8-Mar-2021

Correspondence Address:
Bhawna Sirohi
Department of Medical Oncology, Apollo Proton Cancer Centre, Chennai 600 028, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmr.IJMR_2709_19

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How to cite this article:
Patel A, Sirohi B. Nab-paclitaxel - Third-line chemotherapy in advanced gallbladder cancer. Indian J Med Res 2020;152:442-3

How to cite this URL:
Patel A, Sirohi B. Nab-paclitaxel - Third-line chemotherapy in advanced gallbladder cancer. Indian J Med Res [serial online] 2020 [cited 2021 May 15];152:442-3. Available from: https://www.ijmr.org.in/text.asp?2020/152/5/442/310885

Gall bladder cancer (GBC) is a common cancer for north and north-eastern part of India with incidence ranging from 11.8 to 17.1/100,000 population[1]. Majority of patients present in advanced stages and are eligible only for palliative chemotherapy which has not made a significant difference in improving outcomes[2],[3]. The practice changing studies for the first- and the second-line palliative chemotherapy have included both cholangiocarcinoma and GBC under the umbrella of biliary tract cancers[4].

Talwar et al[5] in their study on Nab-paclitaxel (Nab-P) in advanced GBC made a significant contribution in the management of GBC. The median overall survival (OS) of advanced GBC has been reported to be 4.5 months without treatment[6]. In the subset analysis of ABC0 2 trial[4], no benefit was observed from gemcitabine-cisplatin (Gem-Cis) combination as compared to single-agent gemcitabine, highlighting its importance as a different subset that needs to be looked at separately[3]. Furthermore, given the young median age of patients with GBC at presentation (ranging from 45 to 55 yr) in most studies, it is likely that we will find physically fit patients who will be eligible for second- and third-line treatments[7],[8],[9]. Sharma et al[7] conducted the first randomized controlled trial in GBC wherein Gem-Cis was compared with modified gemcitabine-oxaliplatin (mGemOx) as the first-line treatment. The median progression-free survival (PFS) was five months [95% confidence interval (CI) 3.2-6] with a median OS of 8.5 months for entire study population, highlighting the aggressive clinical course and biology of GBC[7]. The current study[5] had a similar median PFS of 5.5 months (95% CI 3.7-7.4) in first-line setting when gemcitabine-platinum combination was used[5]. Gem-Cis had a median PFS of 7.4 months as compared to 4.4 months in gemcitabine-carboplatin (Gem-Carbo) group. For patients (n=12) who received second-line FOLFOX4, the median PFS was 5.4 months. Only seven patients received single-agent Nab-P, with a response rate of 52.4 per cent. The median PFS in these patients was 2.9 months (95% CI 2-7.8).

There is retrospective as well as prospective evidence to show that FOLFOX is the new standard of care for the treatment of biliary tract cancers in second-line setting but we still do not have a standard for third-line treatment[9],[10]. Results on another second-line chemotherapy regimen CAP-IRI (capecitabine & irinotecan) or FOLFIRI (folinic acid, 5-fluorouracil & irinotecan) also need to be evaluated in a randomized setting[11],[12].

It is commendable that the authors discuss a chemotherapy regimen which is easily accessible in third-line setting for a cancer which is not attractive for studies in the Western world[5]. Less than half of the patients with advanced GBC are eligible for second-line therapy and we assume that even a lesser proportion (likely 20-25%) would be eligible for third-line therapy[7]. Data are emerging on the use of basket trials and immunotherapy[13] but this is out of reach for most patients living in a low- and middle-income group countries.

Nab-P has been studied in advanced biliary tract cancer in phase 2 clinical trial in combination of Gem-Cis in the first-line setting[14]. Of the 60 patients, 13 (22%) had GBC. The median PFS was 11.8 months (95% CI 6-15.6) and the median OS was 19.2 months (95% CI 13.2) - not reached which is unprecedented in biliary tract cancers. Nab-P has also been studied in second- and third-line settings in advanced cholangiocarcinoma[15]. Of the 12 patients, five received Nab-P second-line and seven received third-line. This study showed that the median time to progression was six months (range, 2.1-19.2)[15].

A phase 1 third-line study from Japan on the use of paclitaxel in patients who have failed Gem-Cis and fluoropyrimidine, has shown that this is feasible and effective[16]. The disease control rate in six patients was 83 per cent with a median OS of nine months[16]. Nab-P has been approved in breast cancer, pancreatic cancer and lung cancer in various settings. In view of the rarity of GBC in the Western world, recommendations are not formulated and propagated in international guidelines. National Comprehensive Cancer Network (NCCN) guidelines do not consider any form of therapy in second- or third-line setting[17].

This study[5] had major limitations in view of small number of patients, retrospective design and highly selected group of patients. With such limitations, it is difficult to derive conclusions or make recommendations. However, this study highlighted the proof of concept of activity of Nab-P in selected cases of GBC in Indian patients. Nab-P is an active drug in GBC and must be studied in prospectively designed trials, preferably in the first-line setting in future studies.

Conflicts of Interest: None.

 
   References Top

1.
National Cancer Registry Programme. Consolidated Report of Population Based Cancer Registries: 2012-14. Available from: http://ncdirindia.org/NCRP/ALL_NCRP_REPORTS/PBCR_REPORT_2012_2014/index.htm, accessed on December 19, 2019.  Back to cited text no. 1
    
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Sirohi B, Singh A, Jagannath P, Shrikhande SV. Chemotherapy and targeted therapy for gall bladder cancer. Indian J Surg Oncol 2014; 5 : 134-41.  Back to cited text no. 2
    
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Shukla HS, Sirohi B, Behari A, Sharma A, Majumdar J, Ganguly M, et al. Indian Council of Medical Research Consensus Document for the management of gall bladder cancer. Indian J Med Paediatr Oncol 2015; 36 : 79-84.  Back to cited text no. 3
    
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Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010; 362 : 1273-81.  Back to cited text no. 4
    
5.
Talwar V, Raina S, Goel V, Dash P, Doval DC. Nab-paclitaxel - An effective third line chemotherapy in patients with advanced, unresectable gallbladder cancer. Indian J Med Res 2020; 152 : 475-81.  Back to cited text no. 5
    
6.
Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: A randomized controlled study. J Clin Oncol 2010; 28 : 4581-6.  Back to cited text no. 6
    
7.
Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, et al. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer 2019; 123 : 162-70.  Back to cited text no. 7
    
8.
Sirohi B, Rastogi S, Singh A, Sheth V, Dawood S, Talole S, et al. Use of gemcitabine-platinum in Indian patients with advanced gall bladder cancer. Future Oncol 2015; 11 : 1191-200.  Back to cited text no. 8
    
9.
Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, et al. ABC-06: A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J Clin Oncol 2019; 37 (Suppl 15) : 4003.  Back to cited text no. 9
    
10.
Dodagoudar C, Doval DC, Mahanta A, Goel V, Upadhyay A, Goyal P, et al. FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients. Jpn J Clin Oncol 2016; 46 : 57-62.  Back to cited text no. 10
    
11.
Ramaswamy A, Ostwal V, Pande N, Sahu A, Jandyal S, Ramadwar M, et al. Second-line palliative chemotherapy in advanced gall bladder cancer, CAP-IRI: Safe and effective option. J Gastrointest Cancer 2016; 47 : 305-12.  Back to cited text no. 11
    
12.
Sebbagh S, Roux J, Dreyer C, Neuzillet C, de Gramont A, Orbegoso C, et al. Efficacy of a sequential treatment strategy with GEMOX-based followed by FOLFIRI-based chemotherapy in advanced biliary tract cancers. Acta Oncol 2016; 55 : 1168-74.  Back to cited text no. 12
    
13.
Turkes F, Carmichael J, Cunningham D, Starling N. Contemporary tailored oncology treatment of biliary tract cancers. Gastroenterol Res Pract 2019; 2019 : 7698786.  Back to cited text no. 13
    
14.
Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: A phase 2 clinical trial. JAMA Oncol 2019; 5 : 824-30.  Back to cited text no. 14
    
15.
Unseld M, Scheithauer W, Weigl R, Kornek G, Stranzl N, Bianconi D, et al. Nab-paclitaxel as alternative treatment regimen in advanced cholangiocellular carcinoma. J Gastrointest Oncol 2016; 7 : 588-94.  Back to cited text no. 15
    
16.
Tajima H, Ohta T, Shinbashi H, Hirose A, Okazaki M, Yamaguchi T, et al. Phase I study of weekly palliative chemotherapy with low-dose third-line paclitaxel for biliary tract cancer. Mol Clin Oncol 2017; 6 : 753-7.  Back to cited text no. 16
    
17.
National Comprehensive Cancer Network. NCCN Guidelines for Hepatobiliary Cancers. Available from: https://www.nccn.org/professionals/physician_gls/default.aspx#hepatobiliary, accessed on December 18, 2019.  Back to cited text no. 17
    




 

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