Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors

Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

doi:10.1001/jamaoncol.2017.0324

Cited by 52 publications

(56 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No patients among the 12 with BS were able to complete the MC, and only one patient could be considered in SD. In addition, Pramanik et al compared MC and supportive care in progressive pediatric solid malignant tumors and found that median PFS and OS were similar in both groups with BS. Lastly, a recent study, investigating the efficacy of the addition of MC to standard chemotherapy versus standard chemotherapy alone in patients with nonmetastatic high‐grade operable osteosarcoma, demonstrated that the addition of MC with methotrexate and cyclophosphamide was not statistically superior to the standard treatment without MC (5‐year PFS = 61% vs 64%, P = 0.395; 5‐year OS = 76% vs 73%, P = 0.539).…”

Section: Discussionmentioning

confidence: 99%

SFCE METRO‐01 four‐drug metronomic regimen phase II trial for pediatric extracranial tumor

Heng-Maillard

Verschuur

Aschero

et al. 2019

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Objective To investigate the antitumor activity of a four‐drug metronomic chemotherapy (MC) regimen in relapsed/progressing pediatric extracranial solid tumors (EST). The primary objective was clinical benefit (complete response /partial response/stable disease [SD]) after two cycles of therapy (four months). Methods Patients aged ≥4 to 25 years with progressing EST and adequate organ function were eligible. Treatment consisted of an eight‐week cycle of oral celecoxib b.i.d., weekly vinblastine, and oral cyclophosphamide for three weeks alternating with oral methotrexate for three weeks, with a two‐week rest. The Kepner–Chang two‐stage model was used with 10 patients in the first stage. If primary objective was reached in two or more patients, eight additional patients were included according to four groups: neuroblastoma (NBL), soft‐tissue sarcoma (STS), bone sarcoma (BS), and miscellaneous (Misc.). Results Forty‐four patients were evaluable. The NBL cohort could be expanded to 18 patients: 4 of 18 patients stabilized with MC treatment for 6 (n = 1) and 12 (n = 3) months. In STS, two of seven patients (metastatic hemangioendothelioma and angiosarcoma) had SD for > 2 cycles. One of nine Misc. (metastatic myoepithelial carcinoma) had SD for one year. All patients with BS had progressive disease. One‐year progression‐free survival of the whole cohort was 6.8% and one‐year overall survival was 55.3%. Grade 3 toxicity occurred in 18 patients and grade 4 in 15 patients. The most frequent toxicity was hematologic, predominantly neutropenia. Conclusions This MC has no activity in BS and limited though interesting activity in NBL with some patients being stable for > 1 year. It is not possible to conclude activity in STS and Misc.

show abstract

Section: Discussionmentioning

confidence: 99%

SFCE METRO‐01 four‐drug metronomic regimen phase II trial for pediatric extracranial tumor

Heng-Maillard

Verschuur

Aschero

et al. 2019

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

“…For example, in a prospective, Phase II, open‐label, single‐arm, multi‐institutional study evaluating the efficacy of a “5‐drug” oral regimen in 100 patients with recurrent or progressive cancer, clinical efficacy was not demonstrated in bone tumors and high‐grade gliomas (HGGs) . Our own group published the first randomized controlled trial in relapsed refractory solid tumors, and showed that metronomic therapy was no better than placebo; however, subgroup analysis revealed that tumors other than bone sarcoma showed benefit for both progression‐free survival and overall survival (OS) with the use of metronomic therapy. Further, specific tumor‐related studies with metronomics showed that this form of treatment appears to work in neuroblastoma and RMS, but not so in osteosarcoma …”

Section: Clinical Usage In Pediatricsmentioning

confidence: 99%

“…Metronomic studies exclusively focusing on Ewing sarcoma/primitive neuro‐ectodermal tumors are rare. The observed results from mixed‐bag studies show limited utility of metronomics in this disease . Likewise, a single‐arm study of a low‐dose anti‐angiogenic regimen of vinblastine and celecoxib in Ewing sarcoma following completion of treatment revealed limited usefulness as there was excess toxicity .…”

Section: Experience In Individual Pediatric Malignanciesmentioning

confidence: 99%

See 1 more Smart Citation

Metronomic therapy in pediatric oncology: A snapshot

Pramanik

Bakhshi

2019

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used solely or in combination with other modalities such as radiotherapy, maximum tolerated dose chemotherapy, and targeted agents in adjuvant, palliative, as well as maintenance settings. No wonder, the resulting medical literature is extremely heterogeneous. In this review, the authors review and synthesize the published literature in pediatric metronomics giving a glimpse of its history, varied applications, and evolution of this genre of chemotherapy in pediatric cancers. Limitations, future prospects, and grey areas are also highlighted.

show abstract

“…Clinical treatment typically comprises chemically synthesized medicines; however, these are very expensive and often have serious side effects (4)(5)(6). Recently, several studies have reported that some agents that are currently used to promote immunity may also inhibit tumour growth (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Anti‑tumour effects of polysaccharide extracted from Acanthopanaxï¿½senticosus and cell‑mediated immunity

Meng

Pan²,

Liu

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. Acanthopanax senticosus, also known as Siberian ginseng, is widely distributed throughout northern Asia and used in traditional Chinese medicine; it has been reported to prevent a number of diseases. However, the association between the antitumour and immunostimulatory activities of polysaccharide extracted from A. senticosus (ASPS) remains to be elucidated. The aim of the present study was to investigate the anti-tumour and immunomodulatory effects of polysaccharide extracted from ASPS on Crocker sarcoma S 180 , hepatic carcinoma H 22 and uterine cervical carcinoma U 14 tumour cell lines implanted in mice. High performance liquid chromatography, gas chromatography and infrared spectroscopy were used to analyse the monosaccharide composition of ASPS. The monosaccharide composition of ASPS (Arabic candy: Xylose: Glucose: Mannose) was 7.1:22.3:7.6:1.0. On day 0, female Kunming mice, were injected subcutaneously with 1x10 8 tumour cells in 0.2 ml. The inoculated mice were subsequently divided into five groups (10 mice/group) as follows: Model group, treated with normal saline; positive control group, treated with 30 mg/kg cyclophosphamide (CTX); and three treatment groups, treated with 200, 100 or 50 mg/kg ASPS. Non-inoculated mice were divided into the normal group, which was treated with normal saline, and the negative control group, which was treated with 200 mg/kg ASPS (n=10/group). CTX and ASPS were administered intragastrically once daily for 10 days. All mice were sacrificed on day 11. ASPS was observed to have an inhibitory effect on the growth of S 180 , H 22 and U 14 cells in solid and ascites tumour-bearing mice. Serum interleukin (IL)-2 and IL-12 levels were significantly increased in S 180 solid tumour-bearing mice treated with 200 or 100 mg/kg ASPS compared with mice in the normal, control and model groups (P<0.05), whereas serum IL-2 and IL-12 levels were significantly decreased in the cyclophosphamide treatment group compared with the normal, control and model groups (P<0.05). No significant difference in serum levels of tumour necrosis factor-α level was observed between any groups. In S 180 and U 14 solid tumour-bearing mice, no significant differences in serum levels of interferon (INF)-γ level in were observed between groups; however, in H 22 solid tumour-bearing mice, treatment with ASPS significantly increased serum INF-γ compared with the positive control group (P<0.05). The results may provide a basis for the potential application of ASPS in clinical treatment for cancer.

show abstract

Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors

Abstract: clinicaltrials.gov Identifier: NCT01858571.

Cited by 52 publications

References 16 publications

SFCE METRO‐01 four‐drug metronomic regimen phase II trial for pediatric extracranial tumor

SFCE METRO‐01 four‐drug metronomic regimen phase II trial for pediatric extracranial tumor

Metronomic therapy in pediatric oncology: A snapshot

Anti‑tumour effects of polysaccharide extracted from Acanthopanaxï¿½senticosus and cell‑mediated immunity

Contact Info

Product

Resources

About