Current Trends in Pharmacy and Pharmaceutical Chemistry

Online ISSN: 2582-5062

Current Trends in Pharmacy and Pharmaceutical Chemistry is the official Journal of Ateos Foundation of Science Education and Research, hosted and Managed IP Innovative Publications Pvt. Ltd, New Delhi, India. Current Trends in Pharmacy and Pharmaceutical Chemistry is an open access, peer-reviewed quarterly international journal publishing since 2019 and is published under auspices of the Ateos Foundation of Science Education and Research. It aims to uplift researchers, scholars, academicians, and professionals in all academic and scientific disciplines. more...

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Get Permission Nerkar: Osteosarcoma: A review


Introduction

OS is most common malignancy of bone occurring in second decade of life. With advent of chemotherapy the 5 years event free survival has increased from <20% to 60% to 70%. Although not much improvement is evident in survival rate in last three decades.5 The four most promising drugs used in OS are Methotrexate, Cisplatin, Doxorubicin and Ifosfamide. In north America and Europe high dose Methotrexate, Adriamycin and Cisplatin (MAP) are standard and show promising results. Non-HDMtx are being seldom followed now.6

Review and Case Reports

HDMtx-containing triple drug regimen (MAP6, 7, 8

With use of triple regimen containing HDMtx doxorubicin and cisplatin. There should be atleast 3 drugs regimen and as per case studies conducted by many research workers, a conclusion was sought with meta-analysis that there is no specific evidence to approve or disapprove HDMtx in OS. However, the three drug regimens including Mtx with Adriamycin plus cisplatin plus ifosfamide MAP (ifos) increased the survival rates. However as suggested by Rastogi et al, the uses of MAP and MAP (ifos) did not show much difference and also no significant difference with MAP plus etoposide.

Indian scenario with HDMtx chemotherapy regimen9, 10, 11

The HDMtx requires admission, rigorous hydration and leucoverin rescue with associated toxicities. In india, as per the case studies and opinion of Rastogi et al, the cost treatment is not economical and there is lack of facilities to measure Mtx levels. HDMtx is prevalent with 4% risk of renal failure and 2% mortality risk in developed countries. Secondly carboxypeptidase G2 the antidote for methotrexate intoxication is also less available in India.

Table 1

Non-high dose methotrexate containing triple regimens

Patiets

Regimen

Median follow up

% overall survival

12

Cisplatin+doxorubicin+ifosfamide

5.5 years

83 (3 years) 75

32

Cisplatin+doxorubicin+ifosfamide (+ etoposide for per rise)

36 month

86 (2 years) 74

53

Cisplatin+cyclophosphamide+ vincristine+doxorubicin

151 month

71 (5 years) 60.4

32

Cisplatin+doxorubicin+ifosfamide

64 month

69 (5 years) 65

75

Carboplatin+doxorubicin+ifosfamide

5.1 years

78.9 (5 years) 66.7

Rise of non-HDMtx-containing three drug regimens12, 13

Thus, to manage the treatment of OS in resources constrained situations, the three drug regimens containing non-HDMtx are rising and have good outcomes in non-metastatic OS. Majority of the non-HDMtx regimens include cisplatin as main drug OS the backbone and combined with doxorubicin with ifosfamide or cyclophosphamide. As studied by Daw et al., doxorubicin and ifosfamide were combined with carboplatin replacing cisplatin and the resultant survival rates of various regimens have been given table below.

It was concluded that used of carboplatin needed further trials to confirm as being active in multiple drug therapy. The use of carboplatin lessens the risk of hydration (as seen in cisplatin) and lessens the risk of electrolyte imbalance, nephrotoxicity and hearing loss. Thus, carboplatin, adriyamycin, ifofamide multidrug therapy may serve useful which does not include HDMtx.

Indian scenario14

According to data published non-metastatic OS treated non-HDMtx in teartiary care centers. On the back of percentage necrosis, patients with >90% necrosis received 3 cycles of cisplatin and doxorubicin or received cisplatin and doxorubicin alternatively for the next eight cycles in case they were poor response. The patients showed event free survival and overall survival rates at 5 years were 36% and 50% for those receiving two drug regimen (25%) and four drug regimen respectively. Necrosis was not a significant prognostic factor for final outcome. Such outcome includes unusually large tumor size, patients with poor performance status, the use of Non-HDMtx based chemotherapy or the use of double drug therapy.

Fourth drug and three drug regimen10, 11

The use of ifosfamide to MAP chemotherapy i.e. the fourth drug addition to MAP (the three drug regimen) was not much beneficial.

Histologic response neoadjuvant chemotherapy15

The prognostic marker for chemotherapy being percentage necrosis assessment in non-metastatic OS. Patient with >90% necrosis: 5 year event free survival rate of approximately 70% to 80% Patients with <90% necrosis: 40% to 60% 5 years event for survival rate. The ultimate conclusion being ifosfamide or etoposide should be added to the poor responders.16

Conclusion

Thus, at a conclusion double drug regimen, three drug regimen and Non-HDMtx regimen should be compared whoever at some parts of the world the double drug regimen being a standard choice and hence all the regimens should conclude with evidence based clinical trial system.

Source of Funding

None.

Conflict of Interest

None.

References

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G Ottaviani N Jaffe The epidemiology of osteosarcomaCancer Treat Res200915231310.1007/978-1-4419-0284-9_1

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S Ferrari S Smeland M Mercuri F Bertoni A Longhi P Ruggieri Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma GroupsJ Clin Oncol20052334884552

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G Bacci S Ferrari N Delepine F Bertoni P Picci M Mercuri Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatinJ Clin Oncol19981626586310.1200/JCO.1998.16.2.658

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R Banjara V S Kumar S A Khan A Majeed R R Poudel H Kanwat Relationship between height and osteosarcoma at the time of diagnosis in the Indian population: A retrospective studyJ Clin Orthop Turc202114162810.1016/j.jcot.2020.04.014

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S Rastogi A Aggarwal A Tiwari V Sharma Chemotherapy in nonmetastatic osteosarcoma: recent advances and implications for developing countriesJ Glob Oncol201741510.1200/JGO.2016.007336

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P Verma S Jain G Kapoor R Tripathi P Sharma D C Doval IAP Chemotherapy Regimen Is a Viable and Cost-effective Option in Children and Adolescents With Osteosarcoma: A Comparative Analysis With MAP Regimen on Toxicity and SurvivalJ Pediatr Hematol Oncol202143446671

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C M Hattinger M Fanelli E Tavanti S Vella S Ferrari P Picci Advances in emerging drugs for osteosarcomaExpert Opin Emerg Drug201520349551410.1517/14728214.2015.1051965

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C Kumar K Vats S P Lohar A Korde G Samuel Camptothecin enhances cell death induced by 177Lu-EDTMP in osteosarcoma cellsCancer Biother Radiopharm20142983173910.1089/cbr.2014.1663

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G Bacci F Bertoni A Longhi S Ferrari C Forni R Biagini Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity: Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumorCancer2003971230687510.1002/cncr.11456

16 

G Bacci C Forni S Ferrari A Longhi F Bertoni M Mercuri G Neoadjuvant chemotherapy for osteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcomeJ Pediatr Hematol Oncol2003251184553



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Article type

Review Article


Article page

35-37


Authors Details

A.G. Nerkar


Article History

Received : 08-09-2021

Accepted : 27-09-2021


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