Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials

Ntukidem, Nse; Arce-Lara, Carlos; Kraut, Eric H.; Cataland, Spero R.; Bekaii‐Saab, Tanios

doi:10.1007/s00280-009-1036-3

Cited by 5 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By capping its total dose and limiting the individual dose, this toxicity may be markedly reduced. In our experience, we found that when MMC is given at an individual dose of 6 mg/m 2 and capped at a cumulative dose of 36 mg/m 2 , it is safe and tolerable with no reportable cases of TTP/HUS [7]. In various combination studies conducted by our group, this dose/schedule was also found to be associated with noticeable activity in patients with various solid tumor malignancies [8–11].…”

Section: Introductionmentioning

confidence: 99%

A phase I dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies

Bekaii‐Saab

Hill

Campbell

et al. 2009

Cancer Chemother Pharmacol

Self Cite

View full text Add to dashboard Cite

Background Mitomycin C (MMC) produces significant upregulation of thymidine phosphorylase, a principal determinant of the therapeutic index of capecitabine-based treatment, starting 4–6 days after treatment. On the basis of the time-dependency of this upregulation, we performed a phase I dose escalation study of capecitabine and MMC in patients with gastrointestinal malignancies. Methods A total of 29 patients with advanced gastrointestinal malignancies received MMC at 6 mg/m2 on day 1 and capecitabine escalated in four successive patient cohorts of doses 500–1,000 mg/m2/day twice daily on days 8–21, every 28 days. MMC was capped at 36 mg/m2. Results A total of 29 patients were enrolled and 90% had at least one prior treatment in the metastatic setting. There was one DLT, grade 3 hand and foot syndrome, at dose level four. The most common toxicity was fatigue (61%). No patients experienced grade 4 toxicities. Nine patients experienced prolonged stability of disease. Conclusion Capecitabine in combination with MMC in the proposed schedule is well-tolerated with evidence of preliminary activity. The recommended dose for phase II studies are MMC at 6 mg/m2 on day 1 of a 28-day cycle with the dose capped at 36 mg/m2, in combination with capecitabine at 1,000 mg/m2 twice daily on days 8–21.

show abstract

Section: Introductionmentioning

confidence: 99%

A phase I dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies

Bekaii‐Saab

Hill

Campbell

et al. 2009

Cancer Chemother Pharmacol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Below 36mg/m2 MMC no TMA is seen. [10] The mechanism is not clear although direct endothelial damage has been suggested. [4,7,11] MMC induced TMA has never been described after a single HIPEC procedure.…”

Section: Introductionmentioning

confidence: 99%

Thrombotic Microangiopathy Induced by Hyperthermal Intraperitoneal Chemotherapy with Mitomycin C

Köksal¹,

Ginkel²,

Zijlstra³

2011

View full text Add to dashboard Cite

A patient with pseudomyxoma peritonei underwent Hyperthermal Intraperitoneal Chemotherapy (HIPEC) with Mitomycin C after which she developed thrombotic microangiopathy. This syndrome mimicked possi-ble surgical complications. Treatment with plasma exchange resolved the syndrome and the patient recov-ered completely. This is the first description of thrombotic microangiopathy early after a single dose intrap-eritoneal Mitomycin C

show abstract

Mitomycin‐C‐Induced Thrombotic Thrombocytopenic Purpura

Crosara¹,

Qumari

Wall

et al. 2013

Pharmacy Practice and Res

View full text Add to dashboard Cite

Background Although mitomycin‐C has been supplanted by other chemotherapeutic drugs, it is still the drug of choice for anus squamous cell carcinoma. Mitomycin‐C has rarely been reported to cause thrombotic thrombocytopenic purpura with or without haemolytic uraemic syndrome (TTP/HUS). Aim To report a case of probable mitomycin‐C‐induced TTP with associated acute renal failure and severe hypertension. Clinical details A 60‐year‐old Caucasian female was diagnosed with anus squamous cell carcinoma and started on mitomycin‐C, fluorouracil and targeted radiation therapy. After completing this regimen, the patient developed acute kidney injury, thrombocytopenia and hypertension. Kidney biopsy revealed diffuse endocapillary cell proliferation and one glomerulus contained multiple hyaline thrombi with basement membrane double contours. Focal subendothelial and intramural fragmented erythrocytes were present; all of which suggested TTP. The patient was started on high‐dose corticosteroids followed by plasmapheresis. Outcomes The patient's blood pressure, and platelets returned to baseline levels, while her renal function improved partially. Conclusion TTP is a rare but serious adverse effect associated with mitomycin‐C. Discontinuing mitomycin‐C does not resolve TTP; a variety of treatments are required, such as corticosteroids, plasmapheresis, chemotherapeutic drugs and rituximab.

show abstract

Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials

Abstract: In this large pooled analysis, we found MMC, when capped at a cumulative dose of 36 mg/m(2), to be safe and tolerable in combination with capecitabine or irinotecan with no reportable cases of TTP/HUS.

Cited by 5 publications

References 37 publications

A phase I dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies

A phase I dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies

Thrombotic Microangiopathy Induced by Hyperthermal Intraperitoneal Chemotherapy with Mitomycin C

Mitomycin‐C‐Induced Thrombotic Thrombocytopenic Purpura

Contact Info

Product

Resources

About