Temozolomide Partially Effective for Aggressive Pituitary Tumors, But More Study Needed, Case Report Shows

Temozolomide — an oral chemotherapy treatment — may be partially effective for Cushing’s disease patients with aggressive pituitary tumors that do not respond to conventional therapies, a case report suggests.

However, despite initial tumor stabilization with temozolomide treatment, the patient described in the case report died shortly thereafter, indicating a need for further research before temozolomide is established as a first-line therapy for these patients.

The report, “Temozolomide therapy for aggressive pituitary Crooke’s cell corticotropinoma causing Cushing’s Disease — a case report with literature review,” was published in the journal Endokrynologia Polska.

Cushing’s disease is often caused by a tumor in the pituitary gland that secretes high levels of adrenocorticotropic hormone (ACTH). ACTH leads to high levels of cortisol, which causes Cushing’s disease.

While some pituitary tumors grow slowly and remain silent for a long time, some are characterized by rapid and aggressive growth. These fast-growing tumors are usually invasive macroadenomas, or tumors larger than 10 mm, that are highly resistant to therapy.

First-line treatment for a patient with a macroadenoma is neurosurgery to remove the tumor, followed by radiotherapy and pharmacological therapy. However, there is increasing evidence that temozolomide should be considered as first-line therapy.

Researchers in Poland present the case of a 61-year-old man with ACTH-dependent Cushing’s disease caused by a corticotropinoma and treated with temozolomide. Corticotropinoma refers to a type of pituitary adenoma that secretes high levels of ACTH and is highly invasive, has high rates of recurrence, and is resistant to standard therapy.

The patient had classic signs and symptoms of severe hypercortisolism, or excess cortisol in the blood. Laboratory testing showed high levels of ACTH and cortisol, confirming a diagnosis of Cushing’s disease.

Using magnetic resonance imaging (MRI), physicians discovered a tumor in the pituitary gland. The patient then underwent transsphenoidal surgery, a type of surgery performed through the nose to remove pituitary tumors.

The patient, however, continued to display symptoms of severe hypercortisolism and underwent a bilateral adrenalectomy — the removal of both adrenal glands.

Despite the surgery, the tumor continued to grow, causing physicians to conduct another three transsphenoidal surgeries and repeated radiotherapy. Additionally, the patient was continuously treated with ketoconazole for Cushing’s disease symptoms. Unfortunately, his clinical status continued to worsen.

This led physicians to start treatment with temozolomide based on evidence from prior published studies. The patient underwent nine cycles of the treatment.

Amazingly, physicians observed an improvement in both the clinical domain (fewer headaches and improved vision) as well as the biochemical domain (a decrease in the levels of cortisol and ACTH).

Unfortunately, temozolomide treatment did not shrink the tumor. In fact, there was a sudden increase in the size of the tumor after the ninth cycle of temozolomide, leading to treatment discontinuation.

After stopping the treatment, the patient’s condition continued to worsen until he eventually died, likely due to the compression of an important area of the brain caused by the size of the tumor.

Contrary to what is published in literature, results of this case show that temozolomide treatment is associated with a partial response at first, followed by the tumor’s sudden progression.

The investigators suggest that this discrepancy is likely due to the fact that physicians mostly report positive results, with few reporting negative results.

Therefore, before establishing temozolomide as a first-line therapy, “further research on the factors of responsiveness and on novel methods to extend the duration of the effect of TMZ [temozolomide] should be carried out,” the researchers conclude.