Biomedical Engineering Reference
In-Depth Information
8.3.2.5   Clinical Eficacy of Trastuzumab
The.therapeutic.eficacy.and.tolerability.of.trastuzumab.have.been.investigated.in.vari-
ous.studies..The.initial.clinical.trials.investigating.the.safety.of.trastuzumab.were.per-
formed. on. women. with. metastatic. breast. tumors. overexpressing. HER2.. Results. from.
phase.I.and.II.trials.in.patients.demonstrated.that.Herceptin.has.an.acceptable.tolerabil-
ity. proile. and. promising. clinical. eficacy. in. patients. 67 . A. response. rate. of. 15-35%. was.
reported.for.trastuzumab.monotherapy.in.MBC,.showing.that.Herceptin.has.signiicant.
biostatic.activity.as.a.single.agent. 57 .Cobleigh.et.al..reported.a.study.in.which.the.beneit.
of. Herceptin. as. a. single. agent. for. MBC. was. evaluated. 68 . In. the. study,. 222. women. were.
enrolled,.of.whom.all.were.extensively.pretreated,.and.a.quarter.had.received.more.than.
two. prior. therapies. and. two-thirds. had. received. paclitaxel.. Two. hundred. and. thirteen.
patients.received.Herceptin,.and.at.11.months.the.overall.response.rate.was.found.to.be.
15%.by.an.independent.response.evaluation.committee..The.median.response.duration.
was. 8.4. months,. with. an. estimated. median. survival. of. 13. months.. Treatment. was. well.
tolerated,.with.only.two.patients.discontinuing.therapy.due.to.toxicity..In.addition,.the.
side.effects.attributable.to.Herceptin.include.fever,.chills,.pain,.asthenia,.nausea,.vomit-
ing,.and.cardiac.dysfunction.
Herceptin.has.been.approved.for.irst-line.use.in.combination.with.chemotherapy..It.has.
been.found.that.Herceptin.helps.to.increase.the.clinical.beneits,.such.as.response.rate,.time.
to.disease.progression,.and.overall.survival.of.irst-line.chemotherapies,.such.as.paclitaxel,.
docetaxel,. doxorubicin,. and. cisplatin. in. patients. with. HER2-overexpressed. MBC. 54,69,70 .
Several.studies.have.examined.different.trastuzumab-taxane.combinations..For.example,.
higher. response. rates. have. been. reported. for. docetaxel,. which. yielded. a. 73%. response.
rate.in.three.phase.II.trials. 71 .An.increased.response.rate.of.50%-80%.was.reported.when.
trastuzumab.was.combined.with.single-agent.cytotoxic.chemotherapy.in.irst-line.MBC. 72 .
Several.studies.have.evaluated.the.role.of.Herceptin.as.a.preoperative.therapy.in.patients.
with.early-stage.breast.cancer..The.greatest.effect.in.vitro.and.in.vivo.was.seen.with.the.
combination.of.paclitaxel.and.Herceptin. 73 .The.approved.combination.therapy.indication.
for. trastuzumab. is. with. 3-weekly. paclitaxel,. and. after. that,. both. weekly. paclitaxel. and.
docetaxel.regimens.are.widely.used..A.phase.II.study.of.preoperative.Herceptin.in.combi-
nation.with.paclitaxel.was.reported.by.Burstein.et.al.,.and.a.pathologic.complete.response.
rate.of.18%.was.found. 74 .Seidman.et.al..reported.that.women.with.MBC.of.HER2.positive.
or.-negative.responded.differently.to.Herceptin. 75 .In.the.study,.patients.were.treated.with.
standard-dose.trastuzumab.plus.weekly.paclitaxel.(90.mg/m 2 )..As.expected,.toxic.effects.
were.typical.of.single-agent.paclitaxel,.and.cardiac.function.was.preserved.for.at.least.a.
year..The.response.rate.was.81%.in.patients.who.were.HER2.positive.by.IHC.evaluation.
and.43%.in.those.who.were.HER2.negative.
The.success.with.Herceptin.in.the.treatment.of.metastatic.breast.cancer.in.combination.
with.chemotherapy.has.inspired.intensive.studies.on.developing.effective.targeted.drug.
delivery.systems..The.combination.of.trastuzumab.and.chemotherapeutic.agents.such.as.
paclitaxel. and. docetaxel. for. the. treatment. of. HER2-overexpressed. cancer. has. been. sug-
gested.as.a.promising.means.of.targeted.chemotherapy.
8.3.3 Trastuzumab-Conjugated Nanoparticles
Nanoparticles. of. biodegradable. polymers. as. a. drug. delivery. system. have. aroused. con-
tinuous.interest.in.recent.years..Drug-loaded.nanoparticles.have.considerable.potential.to.
provide.an.ideal.solution.for.the.major.problems.encountered.in.chemotherapy..It.has.been.
established.that.nanoparticles.can.become.concentrated.preferentially.in.tumors.by.virtue.
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