Dosimetric predictors of acute bone marrow toxicity in carcinoma cervix — experience from a tertiary cancer centre in India

We have previously considered oxyphenbutazone eye ointment (Tanderil Eye Ointment).1,2 Recently, the Licensing Authority has withdrawn the product licence for oral oxyphenbutazone because of its bone marrow toxicity.3 Oxyphenbutazone eye ointment is used for treating episcleritis: should its licence also be withdrawn?

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Bone Marrow Toxicity in Cancer Treatment

Encyclopedia of Radiation Oncology ◽

10.1007/978-3-540-85516-3_285 ◽

2013 ◽

pp. 41-43

Author(s):

Stephan Mose ◽

Brandon J. Fisher ◽

Iris Rusu ◽

Charlie Ma ◽

...

Keyword(s):

Bone Marrow ◽

Cancer Treatment ◽

Bone Marrow Toxicity

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High-dose chemotherapy without autologous bone marrow transplantation in melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.12.1811 ◽

1986 ◽

Vol 4 (12) ◽

pp. 1811-1818 ◽

Cited By ~ 11

Author(s):

N S Tchekmedyian ◽

N Tait ◽

D Van Echo ◽

J Aisner

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Karnofsky Performance Status ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

High Dose Chemotherapy ◽

High Dose ◽

Bone Marrow Toxicity ◽

Autologous Bone

High-dose chemotherapy with BCNU, melphalan, or both, followed by autologous bone marrow transplantation (ABMT) has been reported to produce response rates in excess of 60% in patients with advanced melanoma. We tested doses of BCNU associated with reversible bone marrow toxicity and acceptable extramedullary toxicity without the use of ABMT in 19 patients with a diagnosis of advanced malignant melanoma. All patients were evaluable for toxicity and 18 were evaluable for response; one patient had a new primary tumor. The patient population had a median age of 44 years (range, 16 to 71) and a median Karnofsky performance status of 80 (range, 50 to 100). Ten were women and nine were men, all had visceral dominant disease, and none had received previous chemotherapy. Our purpose was to test the feasibility of treatment without ABMT, its toxicity and efficacy, and the possibility of administering sequential repeated courses of therapy. Vincristine was added to the regimen to potentially increase efficacy. Treatment consisted of BCNU (750 mg/m2) and vincristine (2 mg days 1 and 8). Six patients who recovered bone marrow function received melphalan (60 mg/m2) and vincristine (2 mg days 1 and 8). Twenty-two percent (95% confidence limits, 3% to 39%) of patients had remissions (all partial) and these were of short duration. Toxicity was substantial with 16% early lethality and 29% incidence of lethal drug-related complications. Two patients (11%) died toxic after a second course of BCNU. Our results suggest that there is no practical role for high-dose BCNU in the treatment of melanoma.

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Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.5.1495 ◽

1996 ◽

Vol 14 (5) ◽

pp. 1495-1503 ◽

Cited By ~ 45

Author(s):

S J Clarke ◽

J Hanwell ◽

M de Boer ◽

A Planting ◽

J Verweij ◽

...

Keyword(s):

Bone Marrow ◽

Liver Function ◽

Phase I ◽

Thymidylate Synthase ◽

Liver Toxicity ◽

Response To Treatment ◽

Repeated Treatment ◽

Bone Marrow Toxicity ◽

Phase Ii Trials ◽

Advanced Malignancy

PURPOSE To perform a phase I clinical and pharmacologic study of ZD1694 (Tomudex, Alderley Park, United Kingdom), a new folate-based thymidylate synthase (TS) inhibitor, in patients with advanced malignancy. PATIENTS AND METHODS From February 1991 to January 1993, 61 patients with a range of solid tumor received 161 courses of ZD1694 given as a single 15-minute intravenous infusion every 3 weeks, at escalating doses from 0.1 to 3.5 mg/m2. Pharmacokinetic (PK) analysis was performed with the first two courses of treatment. There were 33 men and 28 women with a median age of 53 years (range, 21 to 73). Fifty-five patients (90%) had previously received chemotherapy. RESULTS Reversible liver toxicity and dose-related gastrointestinal (GI) and bone marrow toxicity occurred at > or = 1.6 mg/m2. Liver function usually returned to normal with repeated treatment, but GI and bone marrow toxicities generally became more severe. No renal toxicity was observed. The maximum-tolerated dose (MTD) was 3.5 mg/m2, at which, in addition to antiproliferative toxicities, four of six patients (67%) developed severe malaise that consisted of anorexia, nausea, and asthenia, with rapidly decreasing performance status that limited re-treatment. Abnormal liver function was also seen in four patients (67%). At 3.0 mg/m2, grades III and IV diarrhea were seen in six of 23 patients (26%) and grade IV myelosuppression in two others. Liver toxicity was self-limiting and not associated with severe malaise. Two patients had a partial response to treatment. PK analysis showed that plasma elimination was triexponential, with pronounced variability in the mean terminal half-life (t1/2gamma) for a given dose ranging from 8.2 to 105 hours. There was a linear relationship between dose and both the area under the concentration-time curve (AUC) and maximum concentration (Cmax), but no clear association between these parameters and response or toxicity. CONCLUSION The dose of ZD1694 recommended for phase II trials is 3.0 mg/m2.

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Pulmonary toxicity following total body irradiation for acute lymphoblastic leukaemia: The Ottawa Hospital Cancer Centre (TOHCC) experience

Journal of Radiotherapy in Practice ◽

10.1017/s1460396915000497 ◽

2015 ◽

Vol 15 (1) ◽

pp. 54-60

Author(s):

R. K. Ujaimi ◽

N. Isfahanian ◽

D. J. La Russa ◽

R. Samant ◽

C. Bredeson ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukaemia ◽

Lymphoblastic Leukaemia ◽

Total Body Irradiation ◽

Pulmonary Toxicity ◽

Conditioning Regimen ◽

Cancer Centre ◽

Ottawa Hospital ◽

Radiation Induced ◽

Total Body

AbstractPurposeTo review the incidence of clinically significant pulmonary toxicity following total body irradiation (TBI) as a part of the conditioning regimen for acute lymphoblastic leukaemia (ALL) patients undergoing bone marrow transplantation (BMT) at The Ottawa Hospital Cancer Centre.MethodsThis is a retrospective review of ALL patients who received TBI in The Ottawa Hospital Bone Marrow Transplant Program (TOH-BMT) as part of their conditioning regimen from 1991 to 2011 inclusive. The patients were treated using a locally developed translating-couch irradiation technique. We have analysed all available data for the first 100 days following TBI to determine the incidence of radiation-induced pulmonary toxicities.ResultsOf the total 622 patients undergoing TBI during the specified period, 88 had ALL. Median age at BMT was 30 years and the conditioning regimens varied. A total of 74 (84%) patients received 12 Gy/6 F/BID of TBI. A total of 55 (63%) patients have died, 32 (36%) within the 1st year after BMT. In the 1st year, pulmonary events were reported for 24 (27%) patients, and the follow-up notes were unavailable for seven (8%). Pulmonary toxicities were reported as the cause of death for six patients, five (6%) within the 1st year. It is estimated that the total number of deaths in the 1st year possibly attributed to radiation-induced lung injury was four (4·5%). Eight (9%) patients had symptoms suggestive of non-lethal grade 2–3 radiation-induced pneumonitis.ConclusionsTBI continues to be an important component of the conditioning regimen for ALL patients undergoing BMT, and the incidence of radiation-induced pulmonary injury, using our technique and lung dose, is comparable to the published literature.

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