NEWS HIGHLIGHTS
Published Studies Related to Lysodren (Mitotane)
Effect of mitotane on pituitary corticotrophs in clinically normal dogs. [2006.08]
OBJECTIVE: To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs...
[Mitotane as possible cause of acute intermittent porphyria]. [2011.09.12]
A 54 year-old woman with acute intermittent porphyria (AIP) developed an attack of porphyria after 156 days of treatment with mitotane following a non-radical adrenalectomy for adrenocortical carcinoma. Mitotane therapy was discontinued but the attack of porphyria persisted for more than four months and included episodes with severe metabolic and neurologic toxicities.
Plasma concentrations of o,p'DDD, o,p'DDA, and o,p'DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study. [2011.06]
CONCLUSIONS: Our data confirm the value of o,p'DDD plasma monitoring as well as targeting the 14 mg/liter cutoff level in the therapeutic management of ACC patients. Furthermore, our results suggest additional benefit of higher levels of o,p'DDD and combined measurement of o,p'DDD and o,p'DDA.
High (18)F-FDG uptake by the remaining adrenal gland four months after surgery and initiation of mitotane treatment in two patients with adrenocortical carcinoma. [2011.05]
Two men, one 42 and the other 35 years old were both subjected to adrenalectomy for adrenocortical carcinoma (ACC). Adjuvant treatment with mitotane [o,p-dichloro-diphenyl-dichloroethane, (o,p-DDD)], was initiated following surgery... In conclusion, an abnormal high (18)F-FDG uptake was observed in the contralateral adrenal gland in both our adrenalectomized ACC patients, 4 months after starting mitotane treatment, probably related to mitotane's effect on steroid metabolism, not yet fully understood.
Mitotane has a strong and a durable inducing effect on CYP3A4 activity. [2011.04]
OBJECTIVE: The effects of mitotane on the pharmacokinetics (PK) of co-administered drugs are mostly unknown. The aim of the present study was to describe the effects of mitotane on the PK of the phenotypic probe midazolam and of the tyrosine kinase inhibitor sunitinib... CONCLUSION: Mitotane has a strong and long-lasting inducing effect on CYP3A4 activity, which will result in clinically relevant interactions with multiple drugs since many drugs are metabolized by this enzyme.
Clinical Trials Related to Lysodren (Mitotane)
Efficacy of Adjuvant Mitotane Treatment (ADIUVO) [Recruiting]
Study Rationale Adrenocortical carcinoma (ACC) is a very rare disease with a high risk of
relapse after radical surgery. The efficacy of adjuvant mitotane treatment is suggested by a
retrospective multicenter international study showing that postoperative mitotane treatment
was associated with a significant reduction of the risk of relapse and death. However, these
promising results need confirmation in a randomized prospective study. Caution should be
adopted particularly in patients with low risk of disease relapse, in whom the benefit of
therapy should be weighted against the side effects. Even if an adjuvant treatment seems
justified in patients at high risk of relapse, a randomised prospective study is needed to
assess whether such a treatment is efficacious in patients at low-intermediate risk.
The purpose of the present study is to determine whether adjuvant mitotane treatment is
effective in prolonging the disease free survival in patients with adrenocortical carcinoma
at low-intermediate risk of progression who underwent radical resection
Evaluation of Side Effects of Mitotane [Recruiting]
Mitotane is standard therapy in the treatment of adrenocortical carcinoma. However, many
side effects are not well documented. Therefore, we are aiming at collecting data about side
effects in patients treated with mitotane
Mitotane With or Without IMC-A12 in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery [Recruiting]
RATIONALE: Drugs used in chemotherapy, such as mitotane, work in different ways to stop the
growth of tumor cells, either by killing the cells or by stopping them from dividing.
Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block
the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or
carry tumor-killing substances to them. It is not yet known whether mitotane is more
effective with or without monoclonal antibody IMC-A12 in treating adrenocortical cancer.
PURPOSE: This randomized phase II trial is studying mitotane and IMC-A12 to see how well
they work compared with mitotane alone in treating patients with recurrent, metastatic, or
primary adrenocortical cancer that cannot be removed by surgery.
International Study: Comparison of Two Treatments for Adrenocortical Cancer [Recruiting]
Background:
- There is no medical consensus about the best treatment for advanced adrenocortical
cancer (ACC) that cannot successfully be treated with surgery alone.
- In 2003, the International Consensus Conference on Adrenal Cancer recommended two chemotherapy regimens - etoposide, doxorubicin, cisplatin plus mitotane and
streptozotocin plus mitotane- as the best choices until better data could be obtained.
All the drugs in the two options have been shown effective against advanced ACC, but
they have different side effects.
Objectives:
- To determine which of the chemotherapy regimens described above is best to start with
in patients with ACC that cannot be surgically removed.
- To determine if there is a way to identify which patients will respond to a certain
therapy.
Eligibility:
- Patients 18 years of age and older from the USA, Scandinavia, Germany, Italy, France, The
Netherlands, Belgium, the UK, Canada and Australia who have adrenocortical cancer that
cannot be cured with surgery alone.
Design:
- Chemotherapy: Patients are randomly assigned to start with one of the two study
regimens. Patients whose tumor continues to grow during treatment are offered the
alternative therapy. All patients receive daily tablets of mitotane. In addition, they
have one of the following two regimens:
- Streptozotocin every 3 weeks for up to six cycles. The first cycle is given on days 1,
2, 3, 4 and 5 and subsequent cycles are given on day 1 only.
- Cisplatin plus etoposide plus doxorubicin every 4 weeks for up to six cycles.
Doxorubicin is given on day 1, etoposide is given on days 2, 3 and 4 and cisplatin is
given on days 3 and 4.
- CT scans of the chest, abdomen and pelvis approximately once every 8 weeks.
- Physical examination, routine blood tests and a check of side effects at the start of
each treatment cycle.
- Blood test to determine if the hormones produced by some adrenocortical cancers have
any effect on the immune system.
- Analysis of genetic markers in blood and tumor tissue for comparison with tumor growth
and patient survival to determine if this can help identify which patients will respond
to a certain therapy.
- Optional procedures:
- Storage of blood and tissue samples for future research.
- Completion of quality-of-life questionnaires every 2 months.
A Study of Combination Chemotherapy and Surgical Resection in the Treatment of Adrenocortical Carcinoma: Continuous Infusion Doxorubicin, Vincristine and Etoposide With Daily Mitotane Before and After Surgical Resection [Completed]
Patients who have no response to preoperative chemotherapy and no residual disease following
surgery on Regimen A are treated on Regimen B postoperatively.
The following acronyms are used:
DDD Mitotane, NSC-38721
DOX Doxorubicin, NSC-123127
VCR Vincristine, NSC-67574
VP-16 Etoposide, NSC-141540
Regimen A: 4-Drug Combination Chemotherapy followed by Surgery followed by 4-Drug
Combination Chemotherapy. DDD/DOX/VCR/VP-16; followed by surgical debulking; followed by
DDD/DOX/VCR/VP-16.
Regimen B: Single-Agent Chemotherapy. DDD.
Reports of Suspected Lysodren (Mitotane) Side Effects
Altered State of Consciousness (5),
Adrenal Insufficiency (4),
Cholestasis (3),
Coma (3),
Somnolence (3),
OFF Label USE (3),
Gamma-Glutamyltransferase Increased (3),
Cytolytic Hepatitis (3),
Aggression (3),
Neoplasm Progression (2), more >>
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