Teaching pack: Chemotherapy

Cytotoxics (platinums, taxanes, anthracyclines, antimetabolites, topoisomerase inhibitors) remain curative in several cancers and are the payloads of antibody-drug conjugates. Progress is in dosing, sequencing, biomarker-guided de-escalation, and toxicity mitigation.

• Autologous stem cell transplant (high-dose therapy): Collect the patient's own blood-forming stem cells, give a very high dose of chemotherapy that would otherwise destroy the marrow, then give the cells back to rebuild it.
• Chronotherapy: timing treatment to the body clock: Giving the same drug at a different time of day, because the body clock changes how much damage it does and how well the immune system responds.
• Cytotoxic chemotherapy: Cytotoxic chemotherapy drugs kill rapidly dividing cells. They are still curative in testicular cancer, lymphoma, leukaemia, and many early-stage cancers, and they are the warhead inside ADCs.
• Exercise during chemotherapy and radiotherapy: Moderate exercise while on chemotherapy is safe and reduces fatigue, helps people finish their planned doses, and may protect the heart and nerves.
• Fasting and fasting-mimicking diets around chemotherapy: Eating very little for a few days around each chemotherapy dose might protect normal cells and sensitise the tumour. Early trials are intriguing but small, and it is not something to try without a dietitian.
• Generic oncology drug supply and shortage mitigation: Keeping cheap, essential chemotherapy drugs like cisplatin available; shortages in 2023 forced rationing in US hospitals.
• HIPEC / PIPAC (intraperitoneal chemotherapy): Washing the abdominal cavity with heated chemotherapy during surgery to kill microscopic peritoneal deposits.
• Hypoxia-activated prodrugs: A harmless molecule that turns into a poison only where there is no oxygen, which in the body means inside a tumour.
• Infusion pumps, ports, and ambulatory chemotherapy devices: Infusion devices are the implanted ports, smart pumps, and take-home pumps that deliver chemotherapy safely, including 46-hour infusions patients carry home.
• Metabolic therapy: starving the tumour of a nutrient: Removing an amino acid or nutrient that certain tumours cannot make for themselves, while normal cells can.

• CROSS (phase 3, n=366): Overall survival: 49.4 months vs 24 months, HR 0.68
• PORTEC-3 (phase 3, n=660): Overall survival at 5 years: 81.4% vs 76.1%, HR 0.7
• PERSEUS (phase 3, n=709): Progression-free survival at 48 months: 84.3% vs 67.7%, HR 0.42
• EXTREME (phase 3, n=442): Overall survival: 10.1 months vs 7.4 months, HR 0.8
• ZUMA-7 (phase 3, n=359): Event-free survival (median): 8.3 months vs 2 months, HR 0.4
• INTERLACE (phase 3, n=500): Progression-free survival at 5 years: 72% vs 64%, HR 0.65