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Articles

Safety in Lactation: Anthracyclines and other cytotoxic antibiotics

18 September 2020Anthracycline and related cytostatic antibiotics, whether used as monotherapy or in combination with other antineoplastics, are contra-indicated in breastfeeding because of their cytotoxic action on…

Mitomycin: Cytotoxic Drug Stability Monograph

25 August 2020Stability information is essential for the safe aseptic preparation of mitomycin
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Lactation Safety Information

No
No published evidence of safety
Serious adverse effects reported in adults
Short half-life suggests that resumption of breastfeeding 24-48 hours after a dose may be possible. However, as it is normally given in combination with other cytotoxics, the potential risk to the infant outweighs benefits of breastfeeding
24 September 2020

New Medicines

Low-grade upper tract urothelial cancer (UTUC)

Information

New formulation
UroGen
UroGen

Development and Regulatory status

None
None
Launched
Yes
Dec 20According to its latest annual report, UroGen has no immediate plans to pursue licence applications in the EU or UK. UK development plans are uncertain [8].
Apr 20US launch planned for Jun 20 at a price of $21,376 per dose [7]
Apr 20Approved in US [6].
Dec 19In the latest quarterly report, UroGen does not discuss specific plans for EU development [5].
Dec 19FDA accepts and grants priority review to a New Drug Application (NDA) of mitomycin gel 0.4% (UGN 101), for te treatment of low-grade upper tract urothelial cancer. The FDA assigned a Prescription Drug User Fee Act (PDUFA) action date of 18 April 2020. The submission is supported by data from the PIII OLYMPUS trial [4].
Feb 18FDA has granted fast track and orphan drug status to UGN-101 for the treatment of LG-UTUC [3].

Category

DNA synthesis inhibitor - an RTGel-based formulation of mitomycin 0.4% providing slow-release of the drug.
Bladder cancer is the seventh most common cancer in the UK. About 10,000 people develop bladder cancer in UK each year. In most cases, this develops from the transitional (or urothelial) cells [1].
Low-grade upper tract urothelial cancer (UTUC)
Intravesical

Trial or other data

Oct 19Extension PIIIb trial to evaluate the safety and efficacy of mitomycin in patients treated in the OLYMPUS trial (TC-UT-03), who demonstrated complete response at the Primary Disease Evaluation (PDE) 1 Visit and subsequently have a documented recurrence of low grade upper tract urothelial carcinoma at follow up starts (NCT04006691). The open label trial intends to enrol 30 patients in the US and Israel [4].
Sep 19Final analysis from the PIII OLYMPUS trial in patients with low-grade upper tract urothelial cancer (LG UTUC) demonstrated a complete response (CR) of 59% in 42 of the 71 patients in the intent-to-treat population. The durability of response determined by Kaplan-Meier was 89% at 6 months and 84% at 12 months after primary disease evaluation (PDE). The estimated median time-to-recurrence was 13.0 months. In the phase II OPTIMA study, complete response (CR; 35.3%), partial response (PR; 35.3%) and no response (NR; 29.4%) were reported out of the 17 patients from group A (mitomycin gel 40mg). Of the 16 patients in group B (mitomycin gel 80mg), 87.5% had CR and 12.5% had PR [4].
Feb 19RTGel is a proprietary hydrogel technology which has reverse thermal gelation properties with temperature dependent viscosity that allows gel instillation at lower temperatures in liquid form and solidification at body temperature. The hydrogel is formulated using FDA approved inactive ingredients and can be used to create a sustained release formulation for both new and existing drugs. [3].
Feb 19PIII, open-label, uncontrolled OLYMPUS trial (NCT02793128) recruited 71 patients with low-grade, upper tract urothelial cancer. 61 patients have been included in the analysis so far. 57% complete response at primary disease evaluation, four to six weeks following completion of treatment. All evaluated patients in CR remained disease free for six months. Most treatment emergent side effects considered mild or moderate, and transient. Reported treatment adverse events include ureteral narrowing, hydronephrosis, UTI, flank pain and raised creatinine [2].