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dc.contributor.authorThatcher, Nick
dc.contributor.authorLind, Michael J
dc.contributor.authorMorgenstern, Godfrey R
dc.contributor.authorCarr, T
dc.contributor.authorChadwick, G
dc.contributor.authorJones, R
dc.contributor.authorCraig, P
dc.date.accessioned2010-07-30T13:30:23Z
dc.date.available2010-07-30T13:30:23Z
dc.date.issued1989-04-01
dc.identifier.citationHigh-dose, double alkylating agent chemotherapy with DTIC, melphalan, or ifosfamide and marrow rescue for metastatic malignant melanoma. 1989, 63 (7):1296-302 Canceren
dc.identifier.issn0008-543X
dc.identifier.pmid2646005
dc.identifier.urihttp://hdl.handle.net/10541/108700
dc.description.abstractThirty-seven patients with widely metastatic malignant melanoma were treated with one of three chemotherapy regimens, incorporating high-dose dacarbazine (DTIC). The chemotherapy was followed by autologous bone marrow rescue which was harvested under local anesthesia in 25 of the patients. The three regimens comprised a 24-hour infusion of DTIC (Regimen A for patients less than 45 years of age, 4.3 to 10.5 g/m2; B, if greater than 45 years of age 2.7 to 4.0 g/m2; and later C, if greater than 45 years of age 7.0 to 8.0 g/m2). The second alkylating agent was given at +8 and +16 hours from the start of DTIC. The total doses of the melphalan ranged from 60 to 130 mg/m2 for Regimen A and 30 to 40 mg/m2 for Regimen B. Ifosfamide 5.0 to 8.0 g/m2 was given instead of melphalan in Regimen C. The response rates for the regimens were 81% (25% CR) for A, 27% (11% CR) for B, and 20% (with no complete responders) for Regimen C. There was no statistically significant difference between the three regimens for survival with a median value of 6 months. One of the 16 patients treated with the very high dose Regimen A died of septicemia and three of ten patients in Regimen C died within the first 2 weeks of treatment. There was statistically significant greater myelosuppression, stomatitis, and diarrhea in the very high dosage DTIC and melphalan (Regimen A) compared with the other two regimens. No significant difference in response rate or toxicity was observed for the different dosages escalated within each of the three regimens. Although hematologic and gastrointestinal toxicity were very severe, no unusual side effects were noted except for one episode of severe acute renal failure in the high-dose DTIC and melphalan, Regimen A. Responses occurred mainly in nonvisceral, nodal, and cutaneous sites and occasionally in pulmonary metastases. The Karnofsky performance improved 4 to 6 months after treatment notably with the high-dose DTIC and melphalan therapy. No survival benefit for the combination chemotherapy despite the high dosages was detected and such an approach currently cannot be recommended.
dc.language.isoenen
dc.subjectLung Canceren
dc.subjectCancer Metastasisen
dc.subjectSkin Canceren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAlkylating Agents
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshBone Marrow
dc.subject.meshBone Marrow Transplantation
dc.subject.meshDacarbazine
dc.subject.meshHumans
dc.subject.meshIfosfamide
dc.subject.meshLung Neoplasms
dc.subject.meshMelanoma
dc.subject.meshMelphalan
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Metastasis
dc.subject.meshSkin Neoplasms
dc.titleHigh-dose, double alkylating agent chemotherapy with DTIC, melphalan, or ifosfamide and marrow rescue for metastatic malignant melanoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Christie Hospital, Manchester, England.en
dc.identifier.journalCanceren
html.description.abstractThirty-seven patients with widely metastatic malignant melanoma were treated with one of three chemotherapy regimens, incorporating high-dose dacarbazine (DTIC). The chemotherapy was followed by autologous bone marrow rescue which was harvested under local anesthesia in 25 of the patients. The three regimens comprised a 24-hour infusion of DTIC (Regimen A for patients less than 45 years of age, 4.3 to 10.5 g/m2; B, if greater than 45 years of age 2.7 to 4.0 g/m2; and later C, if greater than 45 years of age 7.0 to 8.0 g/m2). The second alkylating agent was given at +8 and +16 hours from the start of DTIC. The total doses of the melphalan ranged from 60 to 130 mg/m2 for Regimen A and 30 to 40 mg/m2 for Regimen B. Ifosfamide 5.0 to 8.0 g/m2 was given instead of melphalan in Regimen C. The response rates for the regimens were 81% (25% CR) for A, 27% (11% CR) for B, and 20% (with no complete responders) for Regimen C. There was no statistically significant difference between the three regimens for survival with a median value of 6 months. One of the 16 patients treated with the very high dose Regimen A died of septicemia and three of ten patients in Regimen C died within the first 2 weeks of treatment. There was statistically significant greater myelosuppression, stomatitis, and diarrhea in the very high dosage DTIC and melphalan (Regimen A) compared with the other two regimens. No significant difference in response rate or toxicity was observed for the different dosages escalated within each of the three regimens. Although hematologic and gastrointestinal toxicity were very severe, no unusual side effects were noted except for one episode of severe acute renal failure in the high-dose DTIC and melphalan, Regimen A. Responses occurred mainly in nonvisceral, nodal, and cutaneous sites and occasionally in pulmonary metastases. The Karnofsky performance improved 4 to 6 months after treatment notably with the high-dose DTIC and melphalan therapy. No survival benefit for the combination chemotherapy despite the high dosages was detected and such an approach currently cannot be recommended.


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