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

Source: https://onco.cc/roadmaps/chemotherapy-roadmap/  
OnCo record `chemotherapy-roadmap` (Roadmap). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Chemotherapy went from a poison that sometimes worked to the backbone of most cures, and is now being given more precisely: to fewer people, at better doses, and increasingly delivered inside an antibody so that it reaches the tumour and not the whole body.

## Summary

Cytotoxic drugs produced the first cures of disseminated cancer (childhood leukaemia, Hodgkin lymphoma, testicular cancer) by combining agents with different mechanisms so that no single resistance pathway could escape. Platinums, taxanes, anthracyclines, antimetabolites and topoisomerase inhibitors remain curative in several cancers and are the partner that immunotherapy and targeted drugs are added to in most first-line regimens.

The field is now doing three things at once. It is giving chemotherapy to fewer people, using gene-expression tests and residual-disease blood tests to identify who gains nothing from it (TAILORx, RxPONDER, DYNAMIC) and dropping components that add toxicity without benefit (RATHL, SCARLET). It is re-examining dose and schedule, with the FDA's Project Optimus guidance, metronomic oral regimens tested at Tata Memorial, and pharmacogenomic testing before the first dose. And it is moving the cytotoxic payload inside antibody-drug conjugates, which have already replaced chemotherapy as the standard in advanced bladder cancer and parts of breast cancer.

The pace is set by problems that are economic as much as scientific: generic shortages, the absence of any incentive to optimise the dose of an off-patent drug, and the under-measurement of toxicity and quality of life in trials.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-10

## Sources

- FDA final guidance: Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases (August 2024): https://www.fda.gov/regulatory-information/search-fda-guidance-documents/optimizing-dosage-human-prescription-drugs-and-biological-products-treatment-oncologic-diseases
- DeVita and Chu, A history of cancer chemotherapy (Cancer Research 2008): https://doi.org/10.1158/0008-5472.CAN-07-6611

## Connected records

- ideas: [A non-profit manufacturer for generic cancer drugs in chronic shortage](https://onco.cc/ideas/idea-reg-nonprofit-generic-chemo-manufacturer/), [A platform trial of very-low-cost metronomic chemotherapy in LMIC common cancers](https://onco.cc/ideas/idea-acc-metronomic-lmic-platform-trial/), [A prevention programme for chemotherapy nerve damage: SARM1 inhibitors, cooling and compression](https://onco.cc/ideas/idea-moon-neuropathy-prevention-programme/), [A strategic reserve of essential generic cancer drugs to end recurring shortages](https://onco.cc/ideas/idea-reg-generic-chemo-strategic-reserve/), [Dose chemotherapy by muscle mass, not body surface area](https://onco.cc/ideas/idea-bio2-lean-mass-dosing/), [Low-dose olanzapine and generic antiemetic bundles in every guideline and formulary](https://onco.cc/ideas/idea-moon-olanzapine-antiemetic-everywhere/), [Protect hearing from cisplatin in adults as we now do in children](https://onco.cc/ideas/idea-moon-hearing-protection-cisplatin/), [Reduce the dose once the cancer responds: response-adapted de-escalation trials](https://onco.cc/ideas/idea-tr1-response-adapted-dose-reduction/), [Test DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhere](https://onco.cc/ideas/idea-tr1-pre-emptive-pharmacogenomic-testing/), [Validate low-cost metronomic oral regimens in phase 3 and carry them into guidelines](https://onco.cc/ideas/idea-reg-metronomic-lmic-phase3-to-label/)
- roadmaps: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/), [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/), [Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation](https://onco.cc/roadmaps/global-access-roadmap/), [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/), [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Cannabinoids for chemotherapy nausea (dronabinol, nabilone, medical cannabis)](https://onco.cc/technologies/cannabinoids-nausea/), [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Generic oncology drug supply and shortage mitigation](https://onco.cc/technologies/generic-drug-shortage-response/), [Growth factors: G-CSF and febrile neutropenia prevention](https://onco.cc/technologies/g-csf-growth-factors/), [Infusion pumps, ports, and ambulatory chemotherapy devices](https://onco.cc/technologies/infusion-devices-vascular-access/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Oncology pharmacy automation and compounding robots](https://onco.cc/technologies/pharmacy-automation/), [Scalp cooling (cold caps: DigniCap, Paxman)](https://onco.cc/technologies/scalp-cooling/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Dactinomycin (actinomycin D)](https://onco.cc/drugs/dactinomycin/), [Dexrazoxane](https://onco.cc/drugs/dexrazoxane/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Mercaptopurine](https://onco.cc/drugs/mercaptopurine/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Rolapitant](https://onco.cc/drugs/rolapitant/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Sodium thiosulfate (otoprotectant)](https://onco.cc/drugs/sodium-thiosulfate/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Vincristine](https://onco.cc/drugs/vincristine/)
- trials: [APT (adjuvant paclitaxel-trastuzumab)](https://onco.cc/trials/apt-trial/), [CheckMate 649](https://onco.cc/trials/checkmate-649/), [CROSS](https://onco.cc/trials/cross/), [DESTINY-Breast06](https://onco.cc/trials/destiny-breast06/), [DYNAMIC](https://onco.cc/trials/dynamic/), [ECHELON-1](https://onco.cc/trials/echelon-1/), [EORTC 26981 / NCIC CE.3 (Stupp trial)](https://onco.cc/trials/eortc-26981/), [EV-302 / KEYNOTE-A39](https://onco.cc/trials/ev-302/), [INTERLACE](https://onco.cc/trials/interlace/), [KEYNOTE-024 & KEYNOTE-189](https://onco.cc/trials/keynote-024-189/), [Low-dose nivolumab plus metronomic chemotherapy (Tata Memorial)](https://onco.cc/trials/low-dose-nivolumab-tmh/), [Low-dose olanzapine for cancer anorexia (Tata Memorial)](https://onco.cc/trials/olanzapine-appetite-tmh/), [METRO PLUS (Tata Memorial Centre, Varanasi)](https://onco.cc/trials/metro-plus-varanasi/), [NAPOLI 3](https://onco.cc/trials/napoli-3/), [Oral metronomic chemotherapy vs intravenous cisplatin (Tata Memorial)](https://onco.cc/trials/metronomic-vs-cisplatin-tmh/), [POLARIX](https://onco.cc/trials/polarix/), [PRODIGE 24 / CCTG PA6](https://onco.cc/trials/prodige-24/), [RATHL](https://onco.cc/trials/rathl/), [RxPONDER (SWOG S1007)](https://onco.cc/trials/rxponder/), [SCARLET (SWOG S2212)](https://onco.cc/trials/scarlet-s2212/), [TAILORx](https://onco.cc/trials/tailorx/)
- bottlenecks: [Cachexia, toxicity and the limits of the patient](https://onco.cc/bottlenecks/b-cachexia-supportive/), [Most of the world has almost no cancer care](https://onco.cc/bottlenecks/b-global-access/), [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- key papers: [A history of cancer chemotherapy](https://onco.cc/key-papers/paper-devita-cancer-res/), [A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer](https://onco.cc/key-papers/paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004/), [Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials](https://onco.cc/key-papers/paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995/), [Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer](https://onco.cc/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/), [Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer](https://onco.cc/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/), [SWOG 9916: docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer](https://onco.cc/key-papers/paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004/), [TAX 327: docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer](https://onco.cc/key-papers/paper-tannock-tax-327-docetaxel-prednisone-nejm-2004/), [TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel](https://onco.cc/key-papers/paper-de-bono-tropic-cabazitaxel-lancet-2010/)

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JSON: https://onco.cc/api/v1/entities/chemotherapy-roadmap.json