Ayurveda Maintenance Therapy in Recurrent Ovarian Cancer
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2022; 43(05): 434-438
DOI: DOI: 10.1055/s-0041-1740323
Abstract
Despite optimal surgery and first-line platinum-based doublet chemotherapy, approximately 70 to 80% of patients with epithelial ovarian cancers relapse. Two cases of recurrent ovarian cancer (ROC) were treated with non–platinum-based Ayurveda maintenance therapy (AMT) consisting of drugs having a herbal and herbomineral origin. This regimen was followed over a period of 3 years and progression-free survival (PFS) was noted along with platinum-free interval (PFI). Two patients were diagnosed with BRCA1 mutated recurrent high-grade serous ovarian carcinoma and treated with the per-oral AMT regimen labeled as ZINCA-30 in our hospital after completion of standard of care treatment and followed up until progression. The ZINCA-30 regimen comprising Jasada (traditional Zinc preparation), Indukanth kwatham and Curcuma amada powder in combination was prescribed based on Rasayana chikitsa postulated in Ayurveda. The patients were followed up every 3 months. The progression-free survival observed in these patients was 28 months and 45 months, respectively. These two pilot cases suggested an increased platinum-free interval (PFI), improved progression-free survival (PFS) in recurrent ovarian cancer (ROC), with the AMT labeled as ZINCA-30 after chemotherapy.
Keywords
recurrent ovarian cancer - progression-free survival - platinum-free interval - ayurveda maintenance treatment - ZINCA-30Publication History
Article published online:
02 February 2022
© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Abstract
Despite optimal surgery and first-line platinum-based doublet chemotherapy, approximately 70 to 80% of patients with epithelial ovarian cancers relapse. Two cases of recurrent ovarian cancer (ROC) were treated with non–platinum-based Ayurveda maintenance therapy (AMT) consisting of drugs having a herbal and herbomineral origin. This regimen was followed over a period of 3 years and progression-free survival (PFS) was noted along with platinum-free interval (PFI). Two patients were diagnosed with BRCA1 mutated recurrent high-grade serous ovarian carcinoma and treated with the per-oral AMT regimen labeled as ZINCA-30 in our hospital after completion of standard of care treatment and followed up until progression. The ZINCA-30 regimen comprising Jasada (traditional Zinc preparation), Indukanth kwatham and Curcuma amada powder in combination was prescribed based on Rasayana chikitsa postulated in Ayurveda. The patients were followed up every 3 months. The progression-free survival observed in these patients was 28 months and 45 months, respectively. These two pilot cases suggested an increased platinum-free interval (PFI), improved progression-free survival (PFS) in recurrent ovarian cancer (ROC), with the AMT labeled as ZINCA-30 after chemotherapy.
Keywords
recurrent ovarian cancer - progression-free survival - platinum-free interval - ayurveda maintenance treatment - ZINCA-30Introduction
Despite optimal surgery and first-line platinum-based doublet chemotherapy, approximately 70 to 80% of patients with epithelial ovarian cancers show a relapse. The most important features that influence the treatment choice in recurrent ovarian cancer (ROC) with respect to systemic therapy are tumor histology, BRCA mutation status, platinum-free interval (PFI), and previous treatment with an anti-VEGF monoclonal antibody. The presence of germline or somatic BRCA mutations allows platinum-responsive patients to optimize the chemotherapy efficacy and prolong progression-free survival (PFS) using a PARP inhibitor given as maintenance therapy until progression.[1]
Response to platinum re-treatment in recurrent epithelial ovarian cancer is related to PFI. The most preferred and accepted chemotherapy in the treatment of platinum-sensitive (PFI > 6 months) recurrence is platinum-based combination regimens. It is considered that extending the PFI with non-platinum agents may enhance the response and the outcome of subsequent re-challenge with platinum.[2]
Therefore, the exploration for therapies with minimal toxicities to increase the PFS was initiated. Time to relapse is an important prognostic factor in ovarian cancer as subsequent chemoresponse is based on this time interval.[3]
In the doctrines of Ayurveda, the clinical stages and treatments for benign and malignant tumors have been discussed in detail.[4]
Rasayana chikitsa is one of the therapeutic segments of Ayurveda, which helps to improve immunity, consists of compounds having immune-stimulant, immune-modulator effects and hence they restore health.[5] A regimen with drugs having anti-cancer properties and predominant Rasayana herbs and minerals has been described here for the management of ROC.
Methodology
We report the detailed course as elaborated in [Table 1] and the follow-up of Ayurveda maintenance treatment (AMT) labeled as ZINCA-30 in two cases of recurrent high-grade serous ovarian cancer in our institution. Two BRCA mutated patients (refer to [Table 1] for details) of ROC were offered AMT ZINCA-30. These patients after completing the standard chemotherapy were not willing for any conventional maintenance therapy and had opted for ZINCA-30.
Event Chronology |
Patient 1-PSK |
Patient 2-BSK |
|
Age in years |
50 |
48 |
|
Co-morbidity |
Hypothyroidism 10 years |
No |
|
Family history |
Not significant |
Mother: ovarian cancer Brother: non-Hodgkin lymphoma |
|
Cancer antigen 125 (CA 125) at diagnosis |
158 U/mL |
2881 U/mL |
|
Primary cytoreduction surgery |
Total abdominal hysterectomy + bilateral salpingo-oophorectomy + omentectomy on 23/06/2010 |
Total abdominal hysterectomy + bilateral salpingo-oophorectomy + omentectomy on 11/7/2015 |
|
Diagnosis–histopathology report |
Bilateral high-grade serous cyst-adenocarcinoma FIGO stage III-B |
Bilateral grade III serous papillary adenocarcinoma FIGO stage III-B |
|
BRCA mutation |
Positive in intron 16 of the BRCA1 gene C.5074 + 1G > A |
Positive in exon 2 of the BRCA1 gene p.Glu23ValfsTer17 |
|
Previously received cancer therapies |
Chemotherapy 1st line |
6 cycles nanoparticle formulation of paclitaxel + carboplatin, last on 21/12/ 2010 |
6 cycles of paclitaxel + carboplatin last on 29/11/2015 |
Recurrence 1 |
12/03/2013 (PFS: 26 months) |
25/07/2017 (PFS: 20 months) |
|
Chemotherapy 2nd line |
6 cycles of gemcitabine + carboplatin, last on 23/09/2013 |
6 cycles of pegylated liposomal doxorubicin + carboplatin, last on 21/02/2018 |
|
Recurrence 2 |
30/06/2016 (PFS: 33 months) |
— |
|
Chemotherapy 3rd line |
6 cycles of doxorubicin + carboplatin, last on 19/10/ 2016 |
— |
|
Recurrence 3 |
11/01/2018 (PFS: 15 months) |
— |
|
2nd cytoreduction surgery followed by chemotherapy 4th line |
6 cycles of liposomal doxorubicin + carboplatin until 02/07/ 2018 |
— |
|
Ayurveda maintenance treatment ZINCA-30 |
Progression-free survival (PFS) |
Started from 02/07/2018 to 01/11/ 2020 |
Started from 21/05/2018 till the date of latest follow up on 19/11/2021 |
Present status |
Recurrence 02/11/2020 (PFS: 28 months) |
No recurrence until 19/11/2021 (PFS 45 months and continued) |
References:
- Pignata S, C Cecere S, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Ann Oncol 2017; 28 (Suppl. 08) viii51 , viii56
- Chuang Y-T, Chang C-L. Extending platinum-free interval in partially platinum-sensitive recurrent ovarian cancer by a non-platinum regimen: its possible clinical significance. Taiwan J Obstet Gynecol 2012; 51 (03) 336-341
- Soyama H, Takano M, Miyamoto M. et al. Factors favouring long-term survival following recurrence in ovarian cancer. Mol Clin Oncol 2017; 7 (01) 42-46
- Balachandran P, Govindarajan R. Cancer–an ayurvedic perspective. Pharmacol Res 2005; 51 (01) 19-30
- Doshi GM, Une HD, Shanbhag PP. Rasayans and non-rasayans herbs: future immunodrug - Targets. Pharmacogn Rev 2013; 7 (14) 92-96
- Gupta S, Nag S, Aggarwal S, Rauthan A, Warrier N. Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives - a review. J Ovarian Res 2019; 12 (01) 103 DOI: 10.1186/s13048-019-0579-0.
- Jorge S, Swisher EM, Norquist BM. et al. Patterns and duration of primary and recurrent treatment in ovarian cancer patients with germline BRCA mutations. Gynecol Oncol Rep 2019; 29: 113-117
- Aravantinos G, Pectasides D. Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review. J Ovarian Res 2014; 7: 57
- Du Bois A, Floquet A, Kim J. et al. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international intergroup trial (AGO-OVAR16). J Clin Oncol 2013; 31 (Suppl. 18) LBA5503-LBA5503
- Pujade-Lauraine E, Ledermann JA, Selle F. et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. [published correction appears in Lancet Oncol. 2017 Sep;18(9):e510] Lancet Oncol 2017; 18 (09) 1274-1284
- Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol 2018; 81 (01) 17-38
- Pothuri B, O'Cearbhaill R, Eskander R, Armstrong D. Frontline PARP inhibitor maintenance therapy in ovarian cancer: A Society of Gynecologic Oncology practice statement. Gynecol Oncol 2020; 159 (01) 8-12
- Montemorano L, Lightfoot MD, Bixel K. Role of olaparib as maintenance treatment for ovarian cancer: the evidence to date. OncoTargets Ther 2019; 12: 11497-11506
- DiSilvestro P, Alvarez Secord A. Maintenance treatment of recurrent ovarian cancer: is it ready for prime time?. Cancer Treat Rev 2018; 69: 53-65
- Norquist BM, Harrell MI, Brady MF. et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol 2016; 2 (04) 482-490
- Tomao F, D'Incalci M, Biagioli E, Peccatori FA, Colombo N. Restoring platinum sensitivity in recurrent ovarian cancer by extending the platinum-free interval: myth or reality?. Cancer 2017; 123 (18) 3450-3459
- Jorge S, Swisher EM, Norquist BM. et al. Patterns and duration of primary and recurrent treatment in ovarian cancer patients with germline BRCA mutations. Gynecol Oncol Rep 2019; 29: 113-117
- Vayalil PK, Kuttan G, Kuttan R. Rasayanas: evidence for the concept of prevention of diseases. Am J Chin Med 2002; 30 (01) 155-171
- Umrani RD, Paknikar KM. Jasada bhasma, a zinc-based ayurvedic preparation: contemporary evidence of antidiabetic activity inspires development of a nanomedicine. Evid Based Complement Alternat Med 2015; 2015: 193156
- Chavare A, Chowdari P, Ghosh S. et al. Safety and bioactivity studies of Jasad Bhasma and its in-process intermediate in Swiss mice. J Ethnopharmacol 2017; 197: 73-86
- Pal D, Gurjar VK. (2017) Nanometals in Bhasma: ayurvedic medicine. In: Rai, Ph.D M., Shegokar, Ph.D R., eds. Metal Nanoparticles in Pharma. Springer, Cham. doi-org-443.webvpn.fjmu.edu.cn/10.1007/978-3-319-63790-7_17
- Umrani RD, Paknikar KM. Ayurvedic medicine zinc bhasma: physicochemical evaluation, anti-diabetic activity and safety assessment. J Biomed Nanotechnol 2011; 7 (01) 148-149
- Department of AYUSH, Ministry of Health & Family Welfare. The Ayurvedic Formulary of India, Part I. 2nd ed. The Controller of Publications; New Delhi: 2003: 227 , 239
- Bastow M, Kriedt CL, Baldassare J, Shah M, Klein C. Zinc is a potential therapeutic for chemoresistant ovarian cancer. J Exp Ther Oncol 2011; 9 (03) 175-181
- Department of AYUSH, Ministry of Health & Family Welfare. The Ayurvedic Pharmacopeia of India, Part I, Vol V. The Controller of Publications; New Delhi: 2006: 13-15
- Ramachandran C, Lollett IV, Escalon E, Quirin KW, Melnick SJ. Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO2 extract in human glioblastoma cells. J Evid Based Complementary Altern Med 2015; 20 (02) 109-119
- ;Lin YG, Kunnumakkara AB, Nair A. et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-KB pathway. Clinical Cancer Research 13 (11) 3423-3430
- ;Pandey V. ed. Sahastrayog, Kashaya Prakaran, Chap. 1. Verse 171. CCRAS; New Delhi: 1990: 298
- Savrikar SS, Ravishankar B. Bhaishajya Kalpanaa - the Ayurvedic pharmaceutics - an overview. Afr J Tradit Complement Altern Med 2010; 7 (03) 174-184
- Dongre S, Pande S. Need and approach of pharmaceutical standardization of Kwath Kalpana in present scenario-a critique. Int J Ayurveda Pharma Res 2016; 4 (03) 57-60 . Accessed November 26, 2021 at: https://ijapr.in/index.php/ijapr/article/view/321
- Mishra BR, Katre SP. Raktaja Gulma in correlation with modern science conditions. Journal of Ayurveda and Integrated Medical Sciences 2018; 3 (02) 73-77
- George SK, Rajesh R, Kumar S, Sulekha B, Balaram P. A polyherbal ayurvedic drug–Indukantha Ghritha as an adjuvant to cancer chemotherapy via immunomodulation. Immunobiology 2008; 213 (08) 641-649
- Sruthi CV, Vendamirtham S, Sindhu A. from the proceedings of Insight Ayurveda 2013, Coimbatore. 24th and 25th May 2013. PA02.20. A comparative study on the total phenolic content and antioxidant property of two Ayurvedic formulations–Indukantham gritham and Indukantham kashayam. Anc Sci Life 2013; 32 (Suppl. 02) S65 DOI: 10.4103/0257-7941.123886.
Address for correspondence
Pankaj Wanjarkhedkar, MD AyurvedaDepartment of Oncology - VLM Cancer Center; Deenanath Mangeshkar Hospital & Research CenterPune, MHIndiaEmail: drwpankaj@gmail.comPublication History
Article published online:
02 February 2022© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
References:
- Pignata S, C Cecere S, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Ann Oncol 2017; 28 (Suppl. 08) viii51 , viii56
- Chuang Y-T, Chang C-L. Extending platinum-free interval in partially platinum-sensitive recurrent ovarian cancer by a non-platinum regimen: its possible clinical significance. Taiwan J Obstet Gynecol 2012; 51 (03) 336-341
- Soyama H, Takano M, Miyamoto M. et al. Factors favouring long-term survival following recurrence in ovarian cancer. Mol Clin Oncol 2017; 7 (01) 42-46
- Balachandran P, Govindarajan R. Cancer–an ayurvedic perspective. Pharmacol Res 2005; 51 (01) 19-30
- Doshi GM, Une HD, Shanbhag PP. Rasayans and non-rasayans herbs: future immunodrug - Targets. Pharmacogn Rev 2013; 7 (14) 92-96
- Gupta S, Nag S, Aggarwal S, Rauthan A, Warrier N. Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives - a review. J Ovarian Res 2019; 12 (01) 103 DOI: 10.1186/s13048-019-0579-0.
- Jorge S, Swisher EM, Norquist BM. et al. Patterns and duration of primary and recurrent treatment in ovarian cancer patients with germline BRCA mutations. Gynecol Oncol Rep 2019; 29: 113-117
- Aravantinos G, Pectasides D. Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review. J Ovarian Res 2014; 7: 57
- Du Bois A, Floquet A, Kim J. et al. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international intergroup trial (AGO-OVAR16). J Clin Oncol 2013; 31 (Suppl. 18) LBA5503-LBA5503
- Pujade-Lauraine E, Ledermann JA, Selle F. et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. [published correction appears in Lancet Oncol. 2017 Sep;18(9):e510] Lancet Oncol 2017; 18 (09) 1274-1284
- Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol 2018; 81 (01) 17-38
- Pothuri B, O'Cearbhaill R, Eskander R, Armstrong D. Frontline PARP inhibitor maintenance therapy in ovarian cancer: A Society of Gynecologic Oncology practice statement. Gynecol Oncol 2020; 159 (01) 8-12
- Montemorano L, Lightfoot MD, Bixel K. Role of olaparib as maintenance treatment for ovarian cancer: the evidence to date. OncoTargets Ther 2019; 12: 11497-11506
- DiSilvestro P, Alvarez Secord A. Maintenance treatment of recurrent ovarian cancer: is it ready for prime time?. Cancer Treat Rev 2018; 69: 53-65
- Norquist BM, Harrell MI, Brady MF. et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol 2016; 2 (04) 482-490
- Tomao F, D'Incalci M, Biagioli E, Peccatori FA, Colombo N. Restoring platinum sensitivity in recurrent ovarian cancer by extending the platinum-free interval: myth or reality?. Cancer 2017; 123 (18) 3450-3459
- Jorge S, Swisher EM, Norquist BM. et al. Patterns and duration of primary and recurrent treatment in ovarian cancer patients with germline BRCA mutations. Gynecol Oncol Rep 2019; 29: 113-117
- Vayalil PK, Kuttan G, Kuttan R. Rasayanas: evidence for the concept of prevention of diseases. Am J Chin Med 2002; 30 (01) 155-171
- Umrani RD, Paknikar KM. Jasada bhasma, a zinc-based ayurvedic preparation: contemporary evidence of antidiabetic activity inspires development of a nanomedicine. Evid Based Complement Alternat Med 2015; 2015: 193156
- Chavare A, Chowdari P, Ghosh S. et al. Safety and bioactivity studies of Jasad Bhasma and its in-process intermediate in Swiss mice. J Ethnopharmacol 2017; 197: 73-86
- Pal D, Gurjar VK. (2017) Nanometals in Bhasma: ayurvedic medicine. In: Rai, Ph.D M., Shegokar, Ph.D R., eds. Metal Nanoparticles in Pharma. Springer, Cham. doi-org-443.webvpn.fjmu.edu.cn/10.1007/978-3-319-63790-7_17
- Umrani RD, Paknikar KM. Ayurvedic medicine zinc bhasma: physicochemical evaluation, anti-diabetic activity and safety assessment. J Biomed Nanotechnol 2011; 7 (01) 148-149
- Department of AYUSH, Ministry of Health & Family Welfare. The Ayurvedic Formulary of India, Part I. 2nd ed. The Controller of Publications; New Delhi: 2003: 227 , 239
- Bastow M, Kriedt CL, Baldassare J, Shah M, Klein C. Zinc is a potential therapeutic for chemoresistant ovarian cancer. J Exp Ther Oncol 2011; 9 (03) 175-181
- Department of AYUSH, Ministry of Health & Family Welfare. The Ayurvedic Pharmacopeia of India, Part I, Vol V. The Controller of Publications; New Delhi: 2006: 13-15
- Ramachandran C, Lollett IV, Escalon E, Quirin KW, Melnick SJ. Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO2 extract in human glioblastoma cells. J Evid Based Complementary Altern Med 2015; 20 (02) 109-119
- ;Lin YG, Kunnumakkara AB, Nair A. et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-KB pathway. Clinical Cancer Research 13 (11) 3423-3430
- ;Pandey V. ed. Sahastrayog, Kashaya Prakaran, Chap. 1. Verse 171. CCRAS; New Delhi: 1990: 298
- Savrikar SS, Ravishankar B. Bhaishajya Kalpanaa - the Ayurvedic pharmaceutics - an overview. Afr J Tradit Complement Altern Med 2010; 7 (03) 174-184
- Dongre S, Pande S. Need and approach of pharmaceutical standardization of Kwath Kalpana in present scenario-a critique. Int J Ayurveda Pharma Res 2016; 4 (03) 57-60 . Accessed November 26, 2021 at: https://ijapr.in/index.php/ijapr/article/view/321
- Mishra BR, Katre SP. Raktaja Gulma in correlation with modern science conditions. Journal of Ayurveda and Integrated Medical Sciences 2018; 3 (02) 73-77
- George SK, Rajesh R, Kumar S, Sulekha B, Balaram P. A polyherbal ayurvedic drug–Indukantha Ghritha as an adjuvant to cancer chemotherapy via immunomodulation. Immunobiology 2008; 213 (08) 641-649
- Sruthi CV, Vendamirtham S, Sindhu A. from the proceedings of Insight Ayurveda 2013, Coimbatore. 24th and 25th May 2013. PA02.20. A comparative study on the total phenolic content and antioxidant property of two Ayurvedic formulations–Indukantham gritham and Indukantham kashayam. Anc Sci Life 2013; 32 (Suppl. 02) S65 DOI: 10.4103/0257-7941.123886.