Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas

Abstract

<jats:p>In this study, the authors sought to investigate the response rate and toxicity of carboplatin in patients with progressive low-grade glioma (LGG). Thirty-two patients with progressive LGG were treated with carboplatin at a dosage of 560 mg/m<jats:sup>2</jats:sup>. Treatment was given at 4-week intervals and continued until the disease progressed, unacceptable toxicity supervened, or for 12 additional courses after achieving maximal response. Patients with stable disease were treated with a total of 12 cycles. All patients were treated as outpatients. Patients were evaluated for response to treatment and toxicity.</jats:p> <jats:p>All patients received a minimum of two cycles of carboplatin, and were examined for response. A partial response was achieved in nine patients (28%) and a minimal response in two (6%), for an overall response rate of 34% (11 of 32 patients). Eighteen patients (56%) had stable disease. A partial response was achieved in the nine patients after a median of six cycles (range 4-11 cycles), a minimal response was achieved in the two patients after five cycles. Glioma progression was noted in three patients after three, five, and five cycles, respectively. The 11 patients in whom some response was achieved had either an optic pathway tumor or a juvenile pilocytic astrocytoma. Twenty-six of the 32 patients had those characteristics, making the response rate in that group 42% (11 of 26 patients). Thirty-two patients received a total of 387 cycles of chemotherapy. Hematological toxicity was moderate. Twenty-one patients developed thrombocytopenia (platelet count &lt; 50,000/μl); three patients required one platelet transfusion each. Nine patients developed neutropenia (absolute neutrophil count &lt; 500/μl); one developed fever and required administration of antibiotic agents. One dose adjustment in each of the patients prevented further thrombocytopenia and neutropenia. Two patients with stable disease died of respiratory complications. One patient developed Grade III ototoxicity after receiving five cycles, one patient developed hypersensitivity to carboplatin, and none developed nephrotoxicity.</jats:p> <jats:p>Carboplatin given at a dosage of 560 mg/m<jats:sup>2</jats:sup> every 4 weeks has activity in patients with progressive LGG. This drug regimen is relatively simple and well tolerated. Further investigation and longer follow-up study are warranted.</jats:p>

Leptomeningeal Dissemination of a Low-Grade Brainstem Glioma without Local Recurrence

“…Radiation therapy can give long-term disease stabilization in some cases. Treatment with carboplatin, alone or combined with vincristine, has been reported to achieve durable disease stabilization in patients with primary or recurrent low-grade gliomas, even in young children who were asymptomatic with widespread neuraxis disease7,12,13). The overall prognosis for patients with leptomeningeal dissemination at the time of recurrence appears to be worse than the prognosis for patients with a localized recurrence, and far better than for patients with a malignant brain tumor with dissemination3,10).…”

Diagnosis and management of optic nerve glioma

“…47,48 In their study, Packer et al reported a progression-free survival of 75% at 2 years and 68% at three years; 48 however, subsequent studies using carboplatin-based regimens have shown variable success. [49][50][51][52][53][54] The carboplatin regimens are not associated with major toxicity and appear relatively well tolerated although neutropaenia, thrombocytopaenia and allergic reactions may occur. Other chemotherapeutic agents that have been used in treating optic gliomas include temozolomide 55,56 and a five-drug regimen combination, abbreviated to TPDCV, that comprised 6-thioguanine, procarbazine, didromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosurea (CCNU) and vincristine.…”

Optic pathway gliomas: a review

“…39 Although other chemotherapy regimens have demonstrated efficacy against low-grade gliomas, the Packer regimen remains the most commonly used course of therapy. 31,37,50,57,60 …”