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passages: document
passages: Amonafide : An active agent in the treatment of previously untreated advanced breast cancer -- a cancer and leukemia group B study ( CALGB 8642 ) . Amonafide is a new imide derivative of naphthalic acid . The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials . The drug is extensively metabolized and detected in plasma and urine . Its toxicity has previously been correlated to the formation of an active metabolite , N-acetyl-amonafide . Amonafide was chosen for inclusion in the Cancer and Leukemia Group B ( CALGB ) master metastatic breast cancer protocol . CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil , or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil . The end point of CALGB 8642 is to assess the difference in survival , toxicity , and overall response when limited exposure to Phase II agents precedes standard chemotherapy . This report deals only with amonafide as a Phase II agent . Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed . Patients had to have histologically documented measurable breast cancer and a performance status of 0-1 . Patients could not have had prior chemotherapy for metastatic disease . Prior adjuvant chemotherapy was permitted . Patients could not have visceral crisis . Amonafide was given at 300 mg/m2/day i.v . for 5 days , and repeated at 21-day intervals for a maximum of four cycles . Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof . Toxicity was primarily hematological and bimodal : 32 % had grade 3 or 4 leukopenia and 24 % had grade 3 or 4 thrombocytopenia ; 22 % had no leukopenia and 44 % had no thrombocytopenia . The response rate was 18 % , including one complete response . When response was analyzed by hematological toxicity , there was a 35.7 % response if patients had leukopenia grade 3/4 ( versus 8.3 % , P = 0.08 ) . There was a 50 % response if patients had thrombocytopenia grade 3/4 ( versus 7.1 % , P = < 0.01 ) . We conclude that amonafide is somewhat active in previously untreated breast cancer patients . There may be a steep dose-response curve , based on the significant correlation between myelosuppression and response . Rates of responses in patients adequately dosed ( i.e. , with significant hematotoxicity ) with amonafide ranged from 35 to 50 % . Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping .
entities: 4139
entities: Intervention_Pharmacological
entities: Amonafide :
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entities: Intervention_Pharmacological
entities: Amonafide
entities: 4141
entities: Intervention_Pharmacological
entities: Amonafide
entities: 4142
entities: Intervention_Pharmacological
entities: amonafide
entities: 4143
entities: Intervention_Pharmacological
entities: Amonafide
entities: 4144
entities: Intervention_Pharmacological
entities: amonafide
entities: 4145
entities: Outcome_Physical
entities: survival
entities: 4146
entities: Outcome_Adverse-effects
entities: toxicity
entities: 4147
entities: Outcome_Physical
entities: overall response
entities: 4148
entities: Outcome_Adverse-effects
entities: Toxicity
entities: 4149
entities: Outcome_Adverse-effects
entities: leukopenia
entities: 4150
entities: Outcome_Adverse-effects
entities: thrombocytopenia
entities: 4151
entities: Outcome_Adverse-effects
entities: leukopenia
entities: 4152
entities: Outcome_Adverse-effects
entities: thrombocytopenia
entities: 4153
entities: Outcome_Physical
entities: response rate
entities: 4154
entities: Outcome_Adverse-effects
entities: hematological toxicity
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entities: Outcome_Adverse-effects
entities: leukopenia
entities: 4156
entities: Outcome_Adverse-effects
entities: thrombocytopenia
entities: 4157
entities: Outcome_Physical
entities: Rates of responses
entities: 4158
entities: Participant_Condition
entities: previously untreated advanced breast cancer -- a
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entities: Participant_Condition
entities: previously untreated metastatic breast cancer patients
entities: 4160
entities: Participant_Condition
entities: Patients had to have histologically documented measurable breast cancer and a performance status of 0-1 . Patients could not have had prior chemotherapy for metastatic disease . Prior adjuvant chemotherapy was permitted . Patients could not have visceral crisis .
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entities: Participant_Condition
entities: previously untreated breast cancer patients