Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial

Inclusion Criteria:

1. Male or female patients aged 18 years or older at screening

2. Has provided written informed consent for the trial

3. Patient with American Joint committee on Cancer (AJCC) 8th edition Stage I-IIIcolorectal cancer or Stage I-IIIa NSCLC, as confirmed by histological or cytologicaldiagnosis. In cases where a histological diagnosis is not possible, suspecteddiagnosis through imaging techniques is acceptable.

4. Patient has an American Society of Anaesthesiologists (ASA) score of 1 to 3

5. Scheduled to receive elective, surgical resection with curative intent

6. Surgery expected to last ≥2 hours and expected to require ≥2 nights hospital stay

7. Able to comply with protocol requirements and follow-up procedures

Exclusion Criteria:

1. Confirmed or suspected allergy to propofol, sevoflurane or intravenous lidocaine

2. Patient with significant liver disease (with elevated International Normalised Ratio (INR) or bilirubin and/or low albumin; i.e. Childs-Pugh Score >Class A;

3. Patient at personal or familial risk of malignant hyperthermia or porphyria

4. Patient with a history of other malignancies within the past 5 years. However,patients with malignancies managed with curative therapy and considered to be at lowrisk of recurrence such as treated skin basal cell carcinoma, squamous cellcarcinoma, malignant melanoma ≤1.0mm without ulceration, localised thyroid cancer,cervical carcinoma in situ or prior malignancies with high likelihood of cure (e.g.low grade prostate and breast cancer) may be included in the study

5. Patient has distant metastases

6. Patient with an actual body weight less than 45kg

7. Patients taking the following drugs that are moderate-strong inhibitors of theCYP1A2 and CYP3A4 metabolic pathways within 72 hours prior to surgery: Antibiotics - 'mycin' class: Clarithromycin, Telithromycin, Azithromycin, Erythromycin Antibiotics

• 'floxacin' class Ciprofloxacin (exception: can be used preoperatively within abowel prep regime), Norfloxacin, Levofloxacin, Sparfloxacin Antibiotics - other:Chloramphenicol, Isoniazid Antifungals: Fluconazole, Itraconazole, Ketoconazole,Posaconazole, Voriconazole Antiretrovirals: Atazanavir; Darunavir; Indinavir;Lopinavir; Nelfinavir; Ombitasvir, Paritaprevir, Ritonavir and Saquinavir.Antidepressants/ADHD: Fluvoxamine, Enoxacine. Calcium-channel blockers: Diltiazem,Verapamil Monoclonal Antibodies: Ceritinib, Idelalisib, Lonafarnib, Tucatinib. Otherstrong cytochrome P450 3A4 inhibitors: Cimetidine, Cobicistat; grapefruit juice,Mifepristone, Nefazodone.