Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serum Biomarkers and on PBMCs in Breast Cancer Surgery

NCT03005860 | Withdrawn DMC

• 1 other identifier: PN 219
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery, perioperative stress, anaesthetics and analgesics may modulate the immunosurveillance mechanisms and overwhelm host defences that normally maintain a balance between immunity \& carcinogenesis. This may lead to escape of cancer cells and tilt the scales toward a more protumorigenic microenvironment. Volatile agents, in particular, have been shown to exhibit profound immunosuppressive effects. In comparison, propofol has a favorable profile and inhibits cancer cell activity. Determining "cancer-protective" role of TIVA with propofol presents an exciting window of opportunity that has potential to improve outcomes in cancer patients undergoing resection surgery

Conditions

Female Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Change in baseline levels versus 24 hour postoperative levels (Tpre vs T24h ) of serum HIF-1a and VEGF-C in both groups.

  The primary objective of this study is to compare the potential effects of inhalation anesthetic (Sevoflurane) with intravenous anesthetic agent (Propofol) on preoperative levels versus 24hour postoperative levels (Tpre vs T24h ) of serum Hypoxia Inducible Factor-1 alpha (HIF-1a) and Vascular Endothelial Growth Factor -C (VEGF-C) in patients with breast cancer undergoing resection surgery.

  Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )

Secondary Outcomes (3)

• Change in levels of serum biomarkers HIF-1a & VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups.

  after removal of tumor intraoperative (Ti) and 24 hours after surgery (T24h)

• Change in levels of serum biomarkers TGF-β, IL-17 IFN-g, TNF-a, IL-6 and MMP-2 at the four time points in both groups.

  preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.

• Measure expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells peripheral blood lymphocytes at four time points

  preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.

Study Arms (2)

Fluoromethyl hexafluoroisopropyl ether

ACTIVE COMPARATOR

In Sevoflurane group, anaesthesia will be induced with Thiopental 5 - 7mg/kg, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with sevoflurane 2-2.2 % to maintain a target MAC value between 0.8 \& 1.0.

Drug: Fluoromethyl hexafluoroisopropyl ether; Drug: Fentanyl Citrate; Drug: Atracurium Besylate

2,6 diisopropylphenol

EXPERIMENTAL

In Propofol group, anesthesia will be will be induced with Propofol TCI \[target controlled infusion pump - Injectomat® TIVA Agilia (Fresenius Kabi)\] using Schneider model to achieve target site concentration of 4-6mcg/ml, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with TCI propofol at 3 - 6 mcg/ml as effect site concentration to maintain BIS 40-60.

Drug: 2,6-Diisopropylphenol; Drug: Fentanyl Citrate; Drug: Atracurium Besylate

Interventions

2,6-Diisopropylphenol DRUG

In Propofol group, anesthesia will be induced with Propofol TCI using Schneider model to achieve a target site concentration of 4 - 6 mcg/ml. Propofol TCI to achieve BIS (Bispectral Index) between 40-60.

Also known as: Fresofol 1%, Fresenius Kabi

2,6 diisopropylphenol

Fluoromethyl hexafluoroisopropyl ether DRUG

In Sevoflurane group, anesthesia will be induced with 5 - 7mg/kg thiopental, maintenance with O2 with air 50:50%, sevoflurane 2-2.5 %, Further fentanyl, in increments of 1 mcg/kg - and atracurium 0.15 mg/kg, will be given as indicated by the clinical signs and hemodynamic changes.

Also known as: Sevoflurane

Fluoromethyl hexafluoroisopropyl ether

Fentanyl Citrate DRUG

Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.

Also known as: Verfen 100mcg/2ml, Verve

2,6 diisopropylphenol; Fluoromethyl hexafluoroisopropyl ether

Atracurium Besylate DRUG

Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement

Also known as: Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.

2,6 diisopropylphenol; Fluoromethyl hexafluoroisopropyl ether

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with histopathologically (biopsy/FNAC) proven breast carcinoma with Resectable disease (T 1-4, N 0-1, M 0) \[Stage I-III\].
• Willing for upfront modified radical mastectomy.
• ASA Physical Status 1-2

You may not qualify if:

• use of morphine or on steroid therapy upto 3 months before surgery;
• history of substance abuse or cognitive dysfunction;
• endocrine disorders- diabetes, hypothyroid;
• history of HIV, Hep-B or Hep-C infections;
• Contraindication to analgesics or anaesthetic drugs;
• Pregnant \& lactating women

Sponsors & Collaborators

• Tata Memorial Centre: lead

Study Sites (1)

Tata Memorial Centre

Mumbai, Maharashtra, 400012, India

Location

Related Publications (15)

• Dikshit RP, Yeole BB, Nagrani R, Dhillon P, Badwe R, Bray F. Increase in breast cancer incidence among older women in Mumbai: 30-year trends and predictions to 2025. Cancer Epidemiol. 2012 Aug;36(4):e215-20. doi: 10.1016/j.canep.2012.03.009. Epub 2012 Apr 20.

  PMID: 22521561 RESULT

• Weigelt B, Peterse JL, van 't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 Aug;5(8):591-602. doi: 10.1038/nrc1670.

  PMID: 16056258 RESULT

• Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004 Aug;21(2):137-48. doi: 10.1016/j.immuni.2004.07.017.

  PMID: 15308095 RESULT

• Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012 Mar 15;130(6):1237-50. doi: 10.1002/ijc.26448. Epub 2011 Nov 9.

  PMID: 21935924 RESULT

• Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, Tsukada K, Saiki I. Increased surgical stress promotes tumor metastasis. Surgery. 2003 May;133(5):547-55. doi: 10.1067/msy.2003.141.

  PMID: 12773983 RESULT

• Boomsma MF, Garssen B, Slot E, Berbee M, Berkhof J, Meezenbroek Ede J, Slieker W, Visser A, Meijer S, Beelen RH. Breast cancer surgery-induced immunomodulation. J Surg Oncol. 2010 Nov 1;102(6):640-8. doi: 10.1002/jso.21662.

  PMID: 20677220 RESULT

• Camara O, Kavallaris A, Noschel H, Rengsberger M, Jorke C, Pachmann K. Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells. World J Surg Oncol. 2006 Sep 26;4:67. doi: 10.1186/1477-7819-4-67.

  PMID: 17002789 RESULT

• Divatia JV, Ambulkar R. Anesthesia and cancer recurrence: What is the evidence? J Anaesthesiol Clin Pharmacol. 2014 Apr;30(2):147-50. doi: 10.4103/0970-9185.129990. No abstract available.

  PMID: 24803747 RESULT

• Heaney A, Buggy DJ. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis? Br J Anaesth. 2012 Dec;109 Suppl 1:i17-i28. doi: 10.1093/bja/aes421.

  PMID: 23242747 RESULT

• Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003 Nov;97(5):1331-1339. doi: 10.1213/01.ANE.0000082995.44040.07.

  PMID: 14570648 RESULT

• Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 2002 Oct 28;184(2):165-70. doi: 10.1016/s0304-3835(02)00210-0.

  PMID: 12127688 RESULT

• Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor beta in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010 Nov;113(5):1118-25. doi: 10.1097/ALN.0b013e3181f79a69.

  PMID: 20930611 RESULT

• Xu YJ, Chen WK, Zhu Y, Wang SL, Miao CH. Effect of thoracic epidural anaesthesia on serum vascular endothelial growth factor C and cytokines in patients undergoing anaesthesia and surgery for colon cancer. Br J Anaesth. 2014 Jul;113 Suppl 1:i49-55. doi: 10.1093/bja/aeu148. Epub 2014 Jun 25.

  PMID: 24966150 RESULT

• Wigmore TJ, Mohammed K, Jhanji S. Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis. Anesthesiology. 2016 Jan;124(1):69-79. doi: 10.1097/ALN.0000000000000936.

  PMID: 26556730 RESULT

• Gisterek I, Matkowski R, Kozlak J, Dus D, Lacko A, Szelachowska J, Kornafel J. Evaluation of prognostic value of VEGF-C and VEGF-D in breast cancer--10 years follow-up analysis. Anticancer Res. 2007 Jul-Aug;27(4C):2797-802.

  PMID: 17695450 RESULT

MeSH Terms

Interventions

Propofol; Sevoflurane; Fentanyl; Atracurium

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzylisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Shubhada Chiplunkar

  Tata Memorial Centre

  STUDY CHAIR

• Rajan Badwe

  Tata Memorial Centre

  STUDY CHAIR

• Anuja Bidkar

  Tata Memorial Centre

  STUDY CHAIR

• Reshma Ambulkar

  Tata Memorial Centre

  STUDY CHAIR

• Raghu Thota

  Tata Memorial Centre

  STUDY CHAIR

• Vani Parmar

  Tata Memorial Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head, Department Of Anaesthesia, Critical Care and Pain

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 29, 2016
• Study Start: January 1, 2017
• Primary Completion: October 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 21, 2023

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)