Delayed but Complete Response following Oral Temozolomide Treatment in Melanoma Leptomeningeal Carcinomatosis

Abstract

Isolated leptomeningeal recurrence of melanoma is rare, occurring in 2% of patients with central nervous system involvement secondary to melanoma. The optimal treatment of leptomeningeal carcinomatosis (LMC) in melanoma has not yet been determined and remains a major challenge. We report a melanoma patient who presented with isolated LMC in the form of a new-onset weakness of the lower limbs, paresthesia of the left hand and foot, lumbago and headache. A lumbar puncture and spinal MRI confirmed LMC. The patient was treated with temozolomide 75 mg/m²/day on a 4 weeks on/2 weeks off schedule. After an initial transient clinical deterioration, the patient showed a complete radiological response as well as a dramatic improvement in quality of life. The encouraging clinical response reported here suggests that dose-intensified temozolomide might have significant activity in the treatment of leptomeningeal dissemination of melanoma and may be a valid treatment option for patients who have not been previously exposed to this agent. Moreover, this treatment regimen is extremely well tolerated and obviates the need for repeated intrathecal administrations of chemotherapeutic agents, which are often not well tolerated by patients who have significant co-morbidities due to their disease. As illustrated in this case, response to temozolomide may occur in a delayed manner, highlighting the importance of following temozolomide treatment long enough before determining that it is inefficient in a given patient.

Melanoma central nervous system metastases: current approaches, challenges, and opportunities

“…Treatment options are very limited due to the generally diffuse pattern of involvement, and these patients have been excluded from almost all clinical trials for patients with advanced melanoma (including those for patients with MBMs). There is minimal evidence of clinical benefit from any intervention, although there are case reports of individual patients achieving good outcomes with various therapies (Hottinger et al, 2011;Kim et al, 2015;Pape et al, 2012;Salmaggi et al, 2002;Schaefer et al, 2011;Wilgenhof and Neyns, 2014).…”

Leptomeningeal carcinomatosis from gastric cancer successfully treated by the intrathecal methotrexate plus temozolomide and simultaneous radiotherapy: Case report and literatures review

“…In addition, published case report studies have proven the efficiency of Temozolomide. 25,26 Therefore, oral temozolomide was well-tolerated in this patient.…”

Treatment of leptomeningeal carcinomatosis: Current challenges and future opportunities

“…While cases of LM responses in other solid tumors have been reported [42], there are no prospective trials and no case reports or case series specifically looking at temozolomide in breast cancer LM to our knowledge.…”