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.
Classes: alkylators and platinums (cisplatin, carboplatin, cyclophosphamide), antimetabolites (5-FU, capecitabine, gemcitabine, methotrexate), microtubule agents (paclitaxel, docetaxel, eribulin, vinca alkaloids), topoisomerase inhibitors (irinotecan, doxorubicin, etoposide). Progress is in scheduling (dose-dense), biomarker-guided omission, and packaging as ADC payloads.
How it works
DNA damage, antimetabolite incorporation, or mitotic spindle disruption in dividing cells.
- Curative in several cancers
- Cheap, generic
- Narrow therapeutic index
- Resistance via efflux pumps and DNA repair
An enzyme that starves leukaemia cells of an amino acid they cannot make; a mainstay of childhood ALL therapy for 50 years, with new versions solving allergy and supply problems.
A gentle chemotherapy that switches silenced genes back on. With venetoclax it became the standard for older people with AML who cannot take intensive treatment.
An East German chemotherapy rediscovered in the 2000s that became the backbone partner for rituximab in follicular, mantle cell and Waldenström lymphomas.
Bleomycin is the 'B' in BEP for testicular cancer and ABVD for Hodgkin lymphoma; its unique danger is scarring of the lungs, so lung function is monitored and it is often dropped when safe.
A second taxane that works after docetaxel and beat a second hormone pill head-to-head (CARD).
CAPTEM (capecitabine plus temozolomide) is an all-oral chemotherapy pair that shrinks pancreatic neuroendocrine tumours in about a third of patients.
CAPOX combines oral capecitabine with oxaliplatin as a pill-based alternative to FOLFOX. Three months of it after surgery is enough for many stage III colon cancers.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
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.
A one-week infusion that puts most people with hairy cell leukaemia into remission for years; also used in multiple sclerosis in tablet form.
The two old chemotherapy drugs packed together into tiny fat bubbles at a fixed ratio, which doubled five-year survival in older adults with high-risk AML.
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 intensive chemotherapy that has induced remission in fit AML patients since 1973: seven days of one drug, three of another. Still the backbone that targeted drugs are added to.
The first antibiotic used as an anticancer drug (1954) and still the core of chemotherapy for Wilms tumour, rhabdomyosarcoma and gestational trophoblastic disease.
The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.
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.
A sea-sponge-derived chemotherapy that extended survival in heavily pretreated breast cancer and in liposarcoma, where almost nothing else had.
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
FLOT is the four-drug chemotherapy given before and after surgery for stomach cancer in the West; since 2025 immunotherapy is added to it.
The 1957 chemotherapy that remains the backbone of treatment for bowel, stomach, pancreatic, anal, head and neck and breast cancers, and as a cream for skin precancers.
FOLFIRI is the other backbone bowel-cancer chemotherapy, swapping oxaliplatin for irinotecan. Used first or second line and, since 2026, with the BRAF combination.
FOLFIRINOX is a four-drug chemotherapy combination that, in 2011, became the first treatment to meaningfully extend life in metastatic pancreatic cancer; it is now the standard before and after surgery.
FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.
A versatile chemotherapy used in pancreatic, bladder, lung, ovarian, breast and biliary cancers, in nasopharyngeal cancer, and as a bladder instillation.
Gemcitabine plus cisplatin has been the chemotherapy backbone for bile duct cancer since 2010 and is now given with immunotherapy.
Gemcitabine plus nab-paclitaxel is the gentler of the two standard chemotherapy backbones for pancreatic cancer, and the base on which most new drugs are being tested.
Hydroxyurea is a cheap, decades-old pill that lowers high blood counts in polycythaemia vera and essential thrombocythaemia and is also the main drug for sickle cell disease.
Ifosfamide is an alkylating chemotherapy partnered with doxorubicin in sarcoma and with etoposide in Ewing sarcoma, given with a bladder-protecting drug.
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.
An old chemotherapy pill used when glioblastoma comes back, and the control arm most new glioblastoma drugs must beat.
A marine-derived chemotherapy that jams cancer's gene-reading machinery, approved for relapsed small-cell lung cancer and, since 2025, as first-line maintenance with atezolizumab.
The myeloma chemotherapy that is also the standard high-dose conditioning before autologous transplant, and, delivered directly into the liver's blood supply or the eye, treats uveal melanoma metastases and retinoblastoma.
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.
The chemotherapy given with radiation to cure anal cancer without surgery, used as a bladder instillation after tumour resection, and since 2020-25 in gel form for upper-tract and recurrent bladder cancers.
A relative of the insecticide DDT that is the only drug specific to adrenal cortex cancer; it needs blood-level monitoring and permanent steroid replacement.
NALIRIFOX is a version of FOLFIRINOX using a liposome-wrapped irinotecan, approved in 2024 as a first-line option for metastatic pancreatic cancer.
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.
A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.
Doxorubicin wrapped in a fatty bubble so it reaches tumours with less heart damage; a workhorse of relapsed ovarian cancer.
Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
Platinum plus etoposide has been the chemotherapy backbone of small-cell lung cancer for over 40 years, and is now given with immunotherapy.
Pralatrexate was the first drug approved specifically for relapsed peripheral T-cell lymphoma; about a third of patients respond.
A first-in-class drug that blocks cortisol signalling in tumour cells, approved in 2026 for platinum-resistant ovarian cancer with chemotherapy.
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.
Topotecan is the long-standing second-line chemotherapy for relapsed small-cell lung cancer, and now the comparator that new drugs must beat.
A chemotherapy derived from a sea squirt, used with liposomal doxorubicin in relapsed ovarian cancer in Europe and for sarcomas.
A conditioning chemotherapy given before donor stem-cell transplant in AML and MDS; it was long used in Europe and reached the US in 2025.
An oral chemotherapy pill for bowel cancer that has stopped responding to everything else; with bevacizumab it extends life by about three months.
Vinblastine is the vinca alkaloid in ABVD, the standard Hodgkin lymphoma regimen, and was formerly in the cisplatin combinations that first cured testicular cancer.
A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.
Vinorelbine is a vinca chemotherapy for lung and breast cancer, available orally, and is now part of maintenance therapy that improved survival in childhood rhabdomyosarcoma.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
Patients with high-risk bladder cancer confined to the lining whose disease has not responded to BCG now have a bladder-sparing option that clears the cancer in most cases, delivered through a simple outpatient procedure. It may allow many to avoid or defer cystectomy, a life-changing operation. Whether responses translate into avoided progression and cystectomy over the long term, and how it compares with cystectomy on survival, remain to be shown.
Patients fit enough for cisplatin whose bladder cancer has invaded the muscle wall should now be offered durvalumab with their pre-operative chemotherapy and for about a year after surgery, which improves the chance of cure without compromising the operation. The trial cannot say whether the adjuvant phase is necessary, or how to treat cisplatin-ineligible patients, for whom other trials are ongoing.
For fit patients with newly diagnosed metastatic pancreatic cancer, a FOLFIRINOX-type regimen is now proven to be better than gemcitabine plus nab-paclitaxel, settling a long-standing debate. The absolute gain is about two months of median survival, and the regimen is more toxic for the gut. Whether liposomal irinotecan adds anything over conventional irinotecan (standard FOLFIRINOX) has never been tested head-to-head.
Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.
Patients with operable stage II-III lung cancer without EGFR or ALK alterations should have chemo-immunotherapy discussed before surgery rather than only afterwards. Three pre-operative cycles do not compromise the operation and improve cure rates. Whether to continue immunotherapy after surgery, as the perioperative trials do, and whether patients with pCR need any further treatment, remain open questions.
For stage II-III triple-negative breast cancer, chemotherapy plus pembrolizumab before surgery and pembrolizumab alone afterwards is now the standard approach worldwide, and the survival gain is real, not just a surrogate. It does not apply to stage I disease or to hormone-receptor-positive or HER2-positive cancers. The price is a year of immunotherapy with a meaningful chance of a permanent endocrine side effect such as hypothyroidism or adrenal insufficiency.
Patients with newly diagnosed advanced stomach or oesophageal adenocarcinoma whose tumour is HER2-negative and PD-L1 positive (CPS 5 or more, or at least 1 in some regions) should receive chemotherapy with nivolumab (or pembrolizumab, from KEYNOTE-859), which adds about three months of median survival and doubles the chance of being alive at three years. The benefit in PD-L1-negative tumours is doubtful, and these patients may be better served by chemotherapy alone or by trials.
Patients with head and neck squamous cell cancer that has recurred or spread should be treated first with pembrolizumab: alone if their tumour is strongly PD-L1 positive and they can wait for a slower response, or with chemotherapy if the tumour is bulky or PD-L1 low. Cetuximab-based chemotherapy is no longer the default. Long-term follow-up shows a small but real group of patients alive at four to five years, which was almost unheard of before.
Most patients with newly diagnosed advanced non-squamous lung cancer that lacks a targetable mutation should receive chemotherapy plus pembrolizumab; those with PD-L1 of 50% or more may reasonably receive pembrolizumab alone. About one in five patients is alive at five years, compared with roughly one in ten with chemotherapy alone. Patients with EGFR or ALK alterations were excluded and should have targeted therapy first.
Patients with newly diagnosed glioblastoma who are fit and under about 70 receive six weeks of radiotherapy with daily temozolomide followed by six monthly cycles of temozolomide; this is still the backbone of treatment two decades later. Testing MGMT methylation identifies who benefits most and guides decisions in older patients. Median survival with the regimen remains only around 15-20 months, and no drug since has clearly improved on it, which is why glioblastoma is a priority for new approaches.
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