Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models
Abstract Background Doxorubicin (DXR) hydrochloride (HCl) liposome injection is an important part of the treatment armamentarium for a number of cancers. With growing needs for affordable and effective anticancer treatments, the development of generics is becoming increasingly important to facilitat...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3377-3 |
| _version_ | 1818907898179223552 |
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| author | Vinod Burade Subhas Bhowmick Kuntal Maiti Rishit Zalawadia Harry Ruan Rajamannar Thennati |
| author_facet | Vinod Burade Subhas Bhowmick Kuntal Maiti Rishit Zalawadia Harry Ruan Rajamannar Thennati |
| author_sort | Vinod Burade |
| collection | DOAJ |
| description | Abstract Background Doxorubicin (DXR) hydrochloride (HCl) liposome injection is an important part of the treatment armamentarium for a number of cancers. With growing needs for affordable and effective anticancer treatments, the development of generics is becoming increasingly important to facilitate patient access to vital medications. We conducted studies in relevant mouse models of cancer to compare the preclinical antitumour efficacy and plasma pharmacokinetic profile of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceutical Industries Ltd. (SPIL DXR HCl liposome injection) with Caelyx® (reference DXR HCl liposome injection). Methods Syngeneic fibrosarcoma (WEHI 164)-bearing BALB/c mice and athymic nude mice transplanted with MX-1 human mammary carcinoma xenografts were treated with SPIL DXR HCl liposome injection, reference DXR HCl liposome injection or placebo, to compare tumour volume, antitumour activity (percentage test/control [%T/C] ratio, tumour regression, and specific tumour growth delay) and toxicity (survival and weight changes) in response to treatment. The pharmacokinetic profile of the SPIL and reference product was also studied in syngeneic fibrosarcoma-bearing mice. Results Treatment with either SPIL or reference DXR HCl liposome injection resulted in significant reduction in tumour volume from baseline in both models at all doses tested. High antitumour activity (%T/C ≤ 10) was seen from Day 21 and Day 14 onwards in SPIL and reference DXR HCl liposome injection–treated syngeneic fibrosarcoma-bearing mice, respectively, at 9 mg/kg. Moderate antitumour activity (%T/C ≤ 20) was seen from Day 17 and Day 24 onwards in SPIL and reference DXR HCl liposome injection–treated MX-1-bearing mice, respectively, at 6 mg/kg. No significant differences in tumour volume and %T/C were observed between SPIL and reference DXR HCl liposome injection–treated groups at any dose (p ≥ 0.05). Toxicity profiles were considered to be generally comparable. Evaluation of test/reference (A/B) ratios and 90% confidence intervals (CIs) for peak serum concentration (Cmax) and area under the curve (AUC0-t, and AUC0-∞) demonstrated bioequivalence of SPIL and reference DXR HCl liposome injections. Conclusions Establishing similarity is of critical importance during the development of generic treatments. SPIL and reference DXR HCl liposome injections were shown to be comparable with regards to antitumour activity, toxicity and pharmacokinetics. |
| first_indexed | 2024-12-19T22:02:26Z |
| format | Article |
| id | doaj.art-1f923aa9aef54f2e8c0d72e4da23b7cc |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-19T22:02:26Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-1f923aa9aef54f2e8c0d72e4da23b7cc2022-12-21T20:04:06ZengBMCBMC Cancer1471-24072017-06-0117111210.1186/s12885-017-3377-3Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse modelsVinod Burade0Subhas Bhowmick1Kuntal Maiti2Rishit Zalawadia3Harry Ruan4Rajamannar Thennati5Sun Pharma Advanced Research Company Ltd.Sun Pharmaceutical Industries Ltd.Sun Pharma Advanced Research Company Ltd.Sun Pharma Advanced Research Company Ltd.Sun Pharma Advanced Research Company Ltd.Sun Pharmaceutical Industries Ltd.Abstract Background Doxorubicin (DXR) hydrochloride (HCl) liposome injection is an important part of the treatment armamentarium for a number of cancers. With growing needs for affordable and effective anticancer treatments, the development of generics is becoming increasingly important to facilitate patient access to vital medications. We conducted studies in relevant mouse models of cancer to compare the preclinical antitumour efficacy and plasma pharmacokinetic profile of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceutical Industries Ltd. (SPIL DXR HCl liposome injection) with Caelyx® (reference DXR HCl liposome injection). Methods Syngeneic fibrosarcoma (WEHI 164)-bearing BALB/c mice and athymic nude mice transplanted with MX-1 human mammary carcinoma xenografts were treated with SPIL DXR HCl liposome injection, reference DXR HCl liposome injection or placebo, to compare tumour volume, antitumour activity (percentage test/control [%T/C] ratio, tumour regression, and specific tumour growth delay) and toxicity (survival and weight changes) in response to treatment. The pharmacokinetic profile of the SPIL and reference product was also studied in syngeneic fibrosarcoma-bearing mice. Results Treatment with either SPIL or reference DXR HCl liposome injection resulted in significant reduction in tumour volume from baseline in both models at all doses tested. High antitumour activity (%T/C ≤ 10) was seen from Day 21 and Day 14 onwards in SPIL and reference DXR HCl liposome injection–treated syngeneic fibrosarcoma-bearing mice, respectively, at 9 mg/kg. Moderate antitumour activity (%T/C ≤ 20) was seen from Day 17 and Day 24 onwards in SPIL and reference DXR HCl liposome injection–treated MX-1-bearing mice, respectively, at 6 mg/kg. No significant differences in tumour volume and %T/C were observed between SPIL and reference DXR HCl liposome injection–treated groups at any dose (p ≥ 0.05). Toxicity profiles were considered to be generally comparable. Evaluation of test/reference (A/B) ratios and 90% confidence intervals (CIs) for peak serum concentration (Cmax) and area under the curve (AUC0-t, and AUC0-∞) demonstrated bioequivalence of SPIL and reference DXR HCl liposome injections. Conclusions Establishing similarity is of critical importance during the development of generic treatments. SPIL and reference DXR HCl liposome injections were shown to be comparable with regards to antitumour activity, toxicity and pharmacokinetics.http://link.springer.com/article/10.1186/s12885-017-3377-3AnthracyclineBioequivalenceDoxorubicin HCl liposome injectionIn vivoPreclinical |
| spellingShingle | Vinod Burade Subhas Bhowmick Kuntal Maiti Rishit Zalawadia Harry Ruan Rajamannar Thennati Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models BMC Cancer Anthracycline Bioequivalence Doxorubicin HCl liposome injection In vivo Preclinical |
| title | Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models |
| title_full | Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models |
| title_fullStr | Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models |
| title_full_unstemmed | Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models |
| title_short | Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models |
| title_sort | lipodox r generic doxorubicin hydrochloride liposome injection in vivo efficacy and bioequivalence versus caelyx r doxorubicin hydrochloride liposome injection in human mammary carcinoma mx 1 xenograft and syngeneic fibrosarcoma wehi 164 mouse models |
| topic | Anthracycline Bioequivalence Doxorubicin HCl liposome injection In vivo Preclinical |
| url | http://link.springer.com/article/10.1186/s12885-017-3377-3 |
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