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The leukaemia risk after chemotherapy was described in the era of mustards and etoposide, and it did not stay there. Platinum drugs carry it, PARP inhibitors raise it about two and a half times against placebo, and lenalidomide with oral melphalan raises it nearly fivefold against melphalan alone. The absolute numbers are small, but the choice of partner drug is sometimes a real decision.
What is done about it. For PARP inhibitors, a blood count before and during treatment and investigation of a cytopenia that does not resolve. For myeloma, the finding below changed practice: an alkylator-free partner, or cyclophosphamide instead of oral melphalan, alongside lenalidomide. These are decisions made with the treating team, and the record on choices made at treatment sets out the rest.
Platinum drugs. The SEER analysis of 700,612 adults treated for a first solid cancer between 2000 and 2013 found that use of known leukaemogenic agents in initial chemotherapy "increased substantially since 2000, most notably for gastrointestinal tract cancers (esophagus, stomach, colon, and rectum; 10% in 2000-2001 to 81% during 2012-2013)", driven by platinum compounds. The same analysis found newly emerging raised risks of therapy-related myeloid neoplasm in people treated since 2000 for oesophageal, cervical, prostate and possibly anal cancer, and since the 1990s for bone and joint and endometrial cancer. The second cancer risk of a chemotherapy era is measured a decade after that era begins, which is why the modern figures keep moving.
PARP inhibitors. A meta-analysis pooled 18 placebo-controlled randomised trials covering 7,307 patients. PARP inhibitors raised the risk of myelodysplastic syndrome or acute myeloid leukaemia against placebo, with a Peto odds ratio of 2.63 (95% CI 1.13 to 6.14, p = 0.026) and no heterogeneity between studies. The absolute incidence was 0.73 per cent (0.50 to 1.07; 21 events in 4,533 patients) in the PARP inhibitor groups and 0.47 per cent (0.26 to 0.85; three events in 2,774 patients) in the placebo groups. In the WHO pharmacovigilance database, 178 reported cases were found, 99 of myelodysplastic syndrome and 79 of acute myeloid leukaemia; median treatment duration was 9.8 months (IQR 3.6 to 17.4) and median latency from first exposure 17.8 months (8.4 to 29.2). Of 104 cases reporting an outcome, 47 (45 per cent) ended in death. Most of those patients had already had platinum chemotherapy, so the meta-analysis measures the risk of adding a PARP inhibitor on top of it rather than the risk of the drug alone.
Lenalidomide, and the partner drug. An individual-patient meta-analysis of seven randomised trials in newly diagnosed myeloma covered 3,218 treated patients, 2,620 who received lenalidomide and 598 who did not. The cumulative incidence of any second primary malignancy at five years was 6.9 per cent (5.3 to 8.5) with lenalidomide and 4.8 per cent (2.0 to 7.6) without (hazard ratio 1.55, 1.03 to 2.34, p = 0.037). Split by type, the solid second cancers were not different (3.8 against 3.4 per cent, HR 1.1, 0.62 to 2.00, p = 0.72); the haematological ones were (3.1 per cent, 1.9 to 4.3, against 1.4 per cent, 0.0 to 3.6; HR 3.8, 1.15 to 12.62, p = 0.029). The finding that mattered was which combination carried it: lenalidomide with oral melphalan raised haematological second cancer risk against melphalan alone with a hazard ratio of 4.86 (2.79 to 8.46, p < 0.0001), while lenalidomide with cyclophosphamide (HR 1.26, 0.30 to 5.38) and lenalidomide with dexamethasone (HR 0.86, 0.33 to 2.24) did not. The authors' conclusion was that alternatives such as cyclophosphamide, or alkylator-free combinations, should be considered instead of oral melphalan alongside lenalidomide.
What is not known. Whether the immunotherapies and antibody-drug conjugates now in first-line use carry any such risk is not yet measurable, because the latency is longer than their time in practice. A reader who is told that a new drug has no second cancer risk should know that the usual reason is that nobody has been followed long enough to see one.
Ball-and-stick model from PubChem 2D record (no 3D conformer available). PubChem record
Showing the molecule this term concerns: Cisplatin.
Shares Alkylating agents and therapy-related myeloid neoplasms, Second cancers after treatment: what the risk is, and what is done about it, Secondary malignancy (therapy-related cancer), Myelodysplastic syndromes / neoplasms (MDS) and the tags rejuvenation, survivorship, second-cancers, blood.
Shares Alkylating agents and therapy-related myeloid neoplasms, Second cancers after treatment: what the risk is, and what is done about it, Secondary malignancy (therapy-related cancer), Myelodysplastic syndromes / neoplasms (MDS) and the tags rejuvenation, survivorship, second-cancers, blood.
Shares Alkylating agents and therapy-related myeloid neoplasms, Second cancers after treatment: what the risk is, and what is done about it, Choices made at the time of treatment that change the second cancer risk, Secondary malignancy (therapy-related cancer) and the tags rejuvenation, survivorship, second-cancers.
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Shares Second cancers after treatment: what the risk is, and what is done about it, Secondary malignancy (therapy-related cancer), Survivorship care and late-effects surveillance, Late effects and survivorship toxicity and the tags rejuvenation, survivorship, second-cancers.
Shares Second cancers after treatment: what the risk is, and what is done about it, Choices made at the time of treatment that change the second cancer risk, Secondary malignancy (therapy-related cancer), Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship, second-cancers.
Shares Second cancers after treatment: what the risk is, and what is done about it, Secondary malignancy (therapy-related cancer), Survivorship care and late-effects surveillance, Late effects and survivorship toxicity and the tags rejuvenation, survivorship, second-cancers.