Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Conventional chemotherapy

17 evidence topics · 12 sources

European standard clinical practice: carboplatin and vincristine first line, vinblastine alternative

“The carboplatin and vincristine regimen remains the standard first line systemic treatment for patients with pLGG, with the SIOP LGG 2004 Trial showing a 5-year overall survival and progression-free survival of 89% and 46.1% respectively.” (opens the source at this quote in a new tab)
“Vinblastine monotherapy as first line treatment for patients with pLGG needing chemotherapy is considered the standard of care for the Canadian Group (5-year PFS 42% in non-NF1 patients).” (opens the source at this quote in a new tab)
“Following Hypersensitivity reactions to carboplatin (HSR), first line treatment may continue with Vinblastine until total duration therapy of 70 weeks.” (opens the source at this quote in a new tab)

COG A9952: carboplatin and vincristine versus TPCV in children younger than 10 years

“Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007).” (opens the source at this quote in a new tab)
“The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.” (opens the source at this quote in a new tab)

SIOP-LGG 2004: vincristine and carboplatin with or without etoposide

“Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02-7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.” (opens the source at this quote in a new tab)
“Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively.” (opens the source at this quote in a new tab)
“The addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy.” (opens the source at this quote in a new tab)

Weekly vinblastine in chemotherapy-naive progressive pLGG

“Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years).” (opens the source at this quote in a new tab)
“Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%).” (opens the source at this quote in a new tab)
“Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort.” (opens the source at this quote in a new tab)

Chemotherapy outcomes and toxicities summarized by independent reviewers

“While the 5-year overall survival (OS) with chemotherapy ranges from 86-94% on recent studies, 5-year progression-free survival (PFS) is less favorable at 42-45% in pLGG, with slightly better PFS reported in patients with NF1 (5-yr PFS 69-85%) (9, 10).” (opens the source at this quote in a new tab)
“Chemotherapy regimens including carboplatin and vincristine or single-agent vinblastine are commonplace today, and while the adverse effect profile of these agents is relatively well tolerated, they carry risks of myelosuppression, gastrointestinal toxicity, and peripheral sensory and motor neuropathy (9–11).” (opens the source at this quote in a new tab)

“Standard systemic treatment for pediatric low-grade gliomas (PLGGs) has traditionally been chemotherapy with either carboplatin/vincristine or weekly vinblastine [3,4]. Unfortunately, many patients will progress despite this treatment approach (50%) and a second line of therapy will be needed [3,4].” (opens the source at this quote in a new tab)

Chemotherapy regimens used as the comparator in LOGGIC/FIREFLY-2

“The SIOPe-BTG LGG WG reported a response rate of 29% (24 weeks after treatment start) and a five-year PFS rate of 45% [9], whereas the COG reported a response rate of 35% (end of treatment) and a five-year event-free survival rate of 39% [8]. A single-arm phase 2 study of single-agent vinblastine (VBL) resulted in a 19% response rate and a five-year PFS rate of 53% [10].” (opens the source at this quote in a new tab)
“The Arm 2 VBL regimen comprises VBL (BSA ≥ 0.6 m2: 6 mg/m2/day, without exceeding 10 mg; BSA < 0.6 m2: BSA dose × 1/30 × body weight [kg]/day) administered IV QW in four-week cycles until completion of treatment at 70 weeks.” (opens the source at this quote in a new tab)

Schedule and duration of carboplatin and vincristine in the North American and European protocols

“Consolidation lasted from week 13 to 53 and consisted of 4-week cycles of CV with a total duration of chemotherapy of 12 months.” (opens the source at this quote in a new tab)
“Patients who required systemic therapy were treated with CV for 18 months (10 cycles of consolidation compared to HIT-LGG 1996) and non-NF-1 patients were randomized to receive etoposide as an addition to CV during induction phase of therapy” (opens the source at this quote in a new tab)
“Later on, CV became the most used regimen for newly diagnosed or progressive PLGG around the globe with the reported 5-PFS ranging from 39 to 47%.” (opens the source at this quote in a new tab)

Carboplatin monotherapy as a first-line alternative

“An Australian retrospective study evaluated efficacy of carboplatin monotherapy (560 mg/m2 every 4 weeks) as a first line therapy in 104 patients treated between 1996 and 2013. Patients received a median of 12 doses and 86% of patients achieved disease stabilization or better (CR/PR/SD). A 5-year PFS was 51% with an excellent OS of 97%. Hypothalamic/chiasmatic location was identified as a main factor of poorer prognosis in regards to PFS.” (opens the source at this quote in a new tab)
“Hematological toxicity was predominant with grades 3 and 4 in 55/81 patients and allergic reaction occurred in 11% of patients” (opens the source at this quote in a new tab)
“Hence carboplatin monotherapy proved to be a possible alternative especially in very large regions with long-distance travels to the nearest oncology center. Moreover, there is no peripheral neuropathy risk compared to CV regimen.” (opens the source at this quote in a new tab)

Scale of SIOP-LGG 2004 and the proportion of registered children who received chemotherapy

“Total 3417 patients were enrolled between 2004 and 2012 in 118 institutions from 11 European countries. Out of 497 patients receiving chemotherapy, 249 were randomized to the CV arm.” (opens the source at this quote in a new tab)
“Presence of diencephalic syndrome was identified as the strongest predicting factor for poor PFS and OS.” (opens the source at this quote in a new tab)

Response rate at end of therapy with carboplatin and vincristine in COG A9952

“The overall response rate for CV arm was 50% at the end of therapy (MR 15%, PR 35%) with 5-year EFS 39%.” (opens the source at this quote in a new tab)
“Toxicity was moderately higher in the TPCV arm.” (opens the source at this quote in a new tab)

Duration and tolerability of first-line vinblastine

“The toxicity of vinblastine treatment was minimal, allowing most patients to complete the 70 weeks of treatment (one patient even extended treatment for two years without notable toxicities).” (opens the source at this quote in a new tab)
“Only 2 patients received red blood cell transfusions, and no patient received platelet transfusions.” (opens the source at this quote in a new tab)

Chemotherapy assignment and duration in the SIOP-LGG 2004 UK optic pathway glioma cohort

“Children received extended chemotherapy for 18 months. Children with NF1-OPGs received vincristine and carboplatin (VC). Children with sporadic OPGs were randomised to either VC alone or with etoposide.” (opens the source at this quote in a new tab)
“One hundred seventy-three children with OPGs were enrolled from 21 UK paediatric oncology centres between 2004 and 2012 (Cancer Research UK trial number CRUK/05/012).” (opens the source at this quote in a new tab)

Carboplatin and vincristine doses differ between the North American and European regimens

“Interestingly, the administration schedule and carboplatin dosing differ between North America and Europe” (opens the source at this quote in a new tab)
“Northern American studies established the induction using carboplatin administered at a dose of 175 mg/m2 for 4 consecutive weeks, followed by a 2-week break, and then continued for 4 more weeks. Vincristine at a dose of 1.5 mg/m2 (maximum dose 2 mg) is administered for 10 weeks, concomitant with carboplatin.” (opens the source at this quote in a new tab)
“In contrast to North American CV, carboplatin was administered at a higher dose (550 mg/m2) every 3–4 weeks.” (opens the source at this quote in a new tab)

Infusion schedules of the SIOP LGG 04 and monthly carboplatin protocols

“The SIOP LGG 04 protocol utilizes carboplatin in a dose of 550 mg/m2 infused over 1 hr on weeks 1, 4, 7, 10, 13, 17, 21, 25, and 6-weekly thereafter, along with vincristine weekly for 10 weeks followed by weeks 10, 13, 17, 21, and 25, and then 3 weeks in every 6 thereafter” (opens the source at this quote in a new tab)
“The protocol used for monthly carboplatin was described by Gururangan et al. in a phase II study and involves carboplatin in a dose of 560 mg/m2 infused over 1 hr every 4 weeks for 12 doses.” (opens the source at this quote in a new tab)
“Infusion times for the two protocols were identical (1 hr) as was pre- and post-hydration (30 min each). There was no routine use of corticosteroids or antihistamine in either protocol.” (opens the source at this quote in a new tab)

Vinblastine starting dose was maintained in a minority of participants

“The most frequent and important toxicity was hematological.” (opens the source at this quote in a new tab)
“The initial dose appeared to be high, as only 24% of patients maintained the initial dose of vinblastine (6 mg/m2).” (opens the source at this quote in a new tab)
“Therefore, the recommended initial dose in future clinical trials after this study has been 5 mg/m2.” (opens the source at this quote in a new tab)

Choice of carboplatin over cisplatin and cisplatin dose reduction to limit hearing loss

“Young age at exposure (aged < 5 years) and high cumulative dose (> 400 mg/m2 cisplatin) further increase the risk of developing cisplatin-induced serious hearing loss” (opens the source at this quote in a new tab)
“For this reason, carboplatin has been used most often in the treatment of pediatric LGG with lesser risk of hearing loss” (opens the source at this quote in a new tab)
“If indicated, lowered doses of cisplatin were applied from 90 mg/m2 to 75 mg/m2 per course” (opens the source at this quote in a new tab)

Monthly and weekly carboplatin doses and the planned duration of first-line treatment

“Several different carboplatin-based regimens were used over the study period. Carboplatin was administered either monthly (median dose, 560 mg/m2 per infusion) or weekly (175 mg/m2 per infusion) with or without vincristine with a planned duration of treatment ranging from 12 months to 18 months.” (opens the source at this quote in a new tab)