Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs

The 1948 antifolate that produced the first chemotherapy remissions in childhood leukaemia and the first cure of a solid tumour; still essential in ALL, lymphoma, osteosarcoma and CNS lymphoma.

A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.

One of the most widely used chemotherapy drugs: part of CHOP for lymphoma, AC for breast cancer, VAC for childhood sarcomas, and used to prepare patients for CAR-T and transplant.

The red chemotherapy drug from a soil bacterium that is still the backbone of treatment for sarcoma, lymphoma and breast cancer, limited by cumulative heart damage.

The first antibiotic used as an anticancer drug (1954) and still the core of chemotherapy for Wilms tumour, rhabdomyosarcoma and gestational trophoblastic disease.

Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.

Mercaptopurine is a daily tablet, or a liquid for children, that keeps acute lymphoblastic leukaemia in remission during the long maintenance phase of treatment.

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.

A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.

The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.

The platinum drug that works in bowel cancer where cisplatin does not, the 'OX' in FOLFOX and CAPOX; its cost is nerve damage in hands and feet.

Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.

Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer.

A versatile chemotherapy used in pancreatic, bladder, lung, ovarian, breast and biliary cancers, in nasopharyngeal cancer, and as a bladder instillation.

Irinotecan is a topoisomerase-blocking chemotherapy central to bowel and pancreatic cancer regimens (FOLFIRI, FOLFIRINOX, NALIRIFOX) and to salvage therapy in childhood sarcomas; it carries the same warhead as the deruxtecan ADC payloads.

The only chemotherapy proven to extend life in glioblastoma, given during and after radiation. It works best when the tumour has switched off a repair gene called MGMT.

The 2005 trial that set the treatment every glioblastoma patient still receives. Nothing has replaced it in twenty years.

Injections of filgrastim or its long-acting form pegfilgrastim after chemotherapy make white cells recover faster, cutting the risk of life-threatening infections and allowing chemotherapy on schedule.

Infusion devices are the implanted ports, smart pumps, and take-home pumps that deliver chemotherapy safely, including 46-hour infusions patients carry home.

The two trials that made immunotherapy, alone or with chemotherapy, the first treatment for most advanced lung cancers.

The trial that added immunotherapy to first-line stomach cancer chemotherapy; at five years, 16% of patients with PD-L1-rich tumours were alive versus 6%.

The trial that made chemotherapy plus radiation before surgery the standard for oesophageal cancer; the survival gain was still there ten years later.

Showed that giving the strong four-drug chemotherapy after pancreatic surgery adds years of life for fit patients.

The first head-to-head trial of the two chemotherapy backbones, won narrowly by the four-drug regimen.

Six weeks of cheap, generic chemotherapy before standard chemoradiation cut deaths by 40%, an advance usable anywhere in the world.

Swapping bleomycin for the CD30 ADC in first-line chemotherapy improved survival in advanced Hodgkin lymphoma, the first frontline survival gain in decades.

The trial that improved on R-CHOP for the first time in twenty years, by swapping vincristine for an ADC.

Showed that most women with the commonest breast cancer can safely skip chemotherapy if a gene test says their risk is low or intermediate.

Postmenopausal women with a few positive lymph nodes and a low gene-test score can skip chemotherapy; premenopausal women still benefit from it.

Showed that a blood test can safely halve the number of colon cancer patients given chemotherapy after surgery.

An ultra-sensitive blood test after surgery that detects leftover cancer months before a scan would.

Showed that patients whose PET scan is clear after two cycles can safely drop bleomycin and its lung toxicity.

Tests whether the anthracycline can be dropped from TNBC pre-surgery treatment without losing effect.

For small HER2-positive tumours, a gentle regimen of weekly paclitaxel plus trastuzumab gives excellent cure rates, avoiding harsher chemotherapy.

An antibody-drug conjugate is a guided missile: an antibody homes to the tumour cell, is swallowed, and releases a chemotherapy so potent it could never be given on its own.

Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.

The first TROP2-targeted ADC. It delivers a strong chemotherapy directly to breast and bladder cancer cells and is now a first-line option in triple-negative breast cancer.

Enfortumab vedotin is an ADC against Nectin-4 that, combined with pembrolizumab, nearly doubled survival in advanced bladder cancer.

Nearly doubled survival in advanced bladder cancer, ending 40 years of platinum chemotherapy as the standard.

Moved Enhertu ahead of chemotherapy in hormone-positive breast cancer and extended it to 'ultralow' HER2.

Twenty-five years of trying to make chemotherapy hit only cancer cells, from the unstable first ADC to today's third-generation blockbusters and the fourth generation now in trials.

Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.

Two cheap tablets taken at home matched, and in fact beat, intravenous cisplatin for advanced head and neck cancer in a 422-patient Indian trial, with fewer side effects.

Adding low-cost oral metronomic tablets to standard paclitaxel-carboplatin doubled median survival from 5 to 10 months in a randomised trial run in Varanasi.

A Mumbai trial that added about one-twentieth of the usual dose of the immunotherapy nivolumab to cheap oral chemotherapy and nearly tripled the share of patients alive at one year.

A cheap gene test before starting common chemotherapy identifies people at high risk of severe or fatal side effects so their dose can be lowered. Europe recommends it; many places still do not do it.

Chemotherapy doses are calculated from height and weight, a formula from the 1950s. Doses based on actual muscle mass may cause fewer severe side-effects.

The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.

Indian trials have shown that tiny daily doses of old oral chemotherapy drugs can help patients with head and neck cancer at a cost of a few dollars a month. These regimens should be proven and adopted worldwide.

Frequent tiny doses of cheap old chemotherapy pills have shown surprising benefit in some cancers. A single large trial network in India and Africa could find out where this works and where it does not.

A tightly fitted cap chilled to a few degrees above freezing, worn before, during and after each chemotherapy infusion, narrows the blood vessels of the scalp so less drug reaches the hair roots. In a randomised trial about half of women on taxane-based chemotherapy kept most of their hair, compared with none who went without.

An old antidote proven in two paediatric trials to halve permanent hearing loss from cisplatin, and approved in 2022 as the first drug to prevent a chemotherapy side effect in children.

Cisplatin causes permanent hearing loss. A cheap drug, sodium thiosulfate, protects children; test and roll it out for adults too.

Dexrazoxane protects the heart from the cumulative damage of doxorubicin in women with metastatic breast cancer who need to keep receiving it, and, as Totect, limits tissue destruction when an anthracycline leaks out of a vein.

Protecting the heart from cancer treatments, which is increasingly important as patients live longer.

A randomised trial in India of a 2.5 mg dose of a decades-old, very cheap tablet. Six in ten patients gained more than 5% of their weight, against one in ten on placebo.

A cheap, old antipsychotic at a low dose is one of the best anti-sickness drugs for chemotherapy. Make sure every cancer unit in the world uses it.

Rolapitant (Varubi) is a long-lasting anti-sickness tablet taken once before chemotherapy, alongside a 5-HT3 blocker and dexamethasone, to prevent nausea and vomiting in the days after treatment.

Two synthetic cannabinoid tablets, dronabinol and nabilone, have been approved for chemotherapy nausea since 1985 and can help when standard anti-sickness drugs fail. Modern antiemetics work better for most people, and evidence for herbal cannabis or vaped products is thin.

Nerve damage from taxanes and platinum is common, often permanent and has no approved preventive. Test the most promising candidates head to head in one programme.

Old, cheap drugs with anti-cancer signals never get the trials they need because no one profits from the result.

Keeping cheap, essential chemotherapy drugs like cisplatin available; shortages in 2023 forced rationing in US hospitals.

Cheap, essential chemotherapy drugs like cisplatin run out because making them is not profitable enough. A non-profit maker could guarantee supply at a fair price.

Cancer patients have had treatments delayed because basic chemotherapy drugs ran out. Keeping a national stockpile, like for flu antivirals, would prevent this.

Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.

Seven in ten cancer deaths happen in low- and middle-income countries, where radiotherapy, pathology, surgery and drugs are scarce.

Wasting and treatment intolerance stop many patients from receiving the doses that would work. Treating the patient, not just the tumour, lags far behind.