Treatment of advanced malignant melanoma with high-dose melphalan and autologous bone marrow transplantation

Cornbleet, M. A.; McElwain, T. J.; Kumar, Prashanth; Filshie, Jacqueline; Selby, P.; Carter, R L; Hedley, David W.; Clark, M. L.; Millar, J. L.

doi:10.1038/bjc.1983.196

Cited by 56 publications

(14 citation statements)

References 10 publications

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“…Early exploratory studies with HDT followed by HSCT documented activity against refractory, large localized and disseminated EFT. 4,11,22 Mel has long been the most commonly used agent in HDT regimen for advanced, high-risk EFT. The French Society for Pediatric Oncology has reported excellent results in children with poor prognosis EFT who were treated with BU (600 mg/ m 2 /dose four times a day Â 4 days) and Mel (140 mg/m 2 , given as 70 mg/m 2 /day Â 2 days).…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of the observed steep dose-response curves in vitro, aggressive approaches, consisting of HDT followed by HSCT, have been utilized, using either fractionated TBI plus chemotherapy 8,[18][19][20] or chemotherapy alone. 11,[21][22][23][24][25][26] In early studies carried out at the National Cancer Institute , using higher than standard doses of chemotherapy followed by TBI (8 Gy), the EFS rate declines from 30 to 40% at 3 years and 8,19 to 10% at 6 years. 20 The investigators conclude that patients with poor prognosis ES treated with TBI and autologous BMT were able to achieve CR; however, this study failed to show any survival benefit over nontransplant.…”

Section: Discussionmentioning

confidence: 99%

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High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors

Rosenthal

Bolotin

Shakhnovits

et al. 2008

Bone Marrow Transplant

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The purpose of the study was to evaluate the feasibility and safety of two cycles of high-dose chemotherapy (HDT) followed by autologous hematopoietic SCT (HSCT) in patients with poor prognosis Ewing family of tumors (EFT). Twenty patients with primary metastatic bulky disease or recurrent EFT were enrolled to a treatment protocol with two cycles of HDT and HSCT. Patients tolerated well the first (n ¼ 20) and second (n ¼ 13) cycles, with limited and predictable toxicities. Only one (5%) TRM occurred during the second cycle. Myeloid engraftment occurred at the median of 11 days after both cycles. At 3 years, the overall and EFS were 45% (confidence interval; CI 0.22, 0.69) and 47% (CI 0.25, 0.70), respectively, for the entire group and 58% (CI 0.30, 0.86) for patients who completed two cycles. Dose intensification with two cycles of HDT and HSCT is feasible and safe, with low and acceptable treatmentrelated morbidity and mortality. Adding a second course of therapy does not impair engraftment. However, only 65% of the patients were able to proceed to the second cycle. Further studies are required to define the optimal mode of delivery of HDT and HSCT in treatment of advanced EFT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors

Rosenthal

Bolotin

Shakhnovits

et al. 2008

Bone Marrow Transplant

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“…Bone marrow was harvested according to standard techniques (Cornbleet et al, 1983) and stored at 4°C for 18 patients. In 4 cases it was cryopreserved in liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma

Mbidde

Selby²,

Perren³

et al. 1988

Br J Cancer

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Summary In a series of 22 patients, high dose BCNU (800-1,000 mgm-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return.Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified.The management of high grade glioma is unsatisfactory (Bloom, 1982). Radiotherapy following surgery will prolong survival by several months but long term survivors from grade IV astrocytoma (glioblastoma multiforme) are rare. Conventional chemotherapy has little to offer. These tumours share the relatively poor cellular chemosensitivity of most solid human cancers. In addition penetration of drugs into high grade gliomas is poor. They often have poor vascularisation and probably also a partially intact bloodbrain barrier in parts of the tumour (Workman, 1986).has been tested in conventional doses following surgery and radiotherapy for the treatment of high grade glioma. It gives a small, statistically significant, prolongation of survival but overall results are still poor with a median survival of only 12 months (Walker et al., 1980;Green et al., 1983). The dose of BCNU that can be given is limited by myelosuppression which is characteristically later in onset than that seen with most cytotoxic drugs (Phillips et al., 1986). The dose of BCNU can be increased when it is given with autologous bone marrow transplantation (ABMT) and such high doses of BCNU can produce useful palliative effects in patients whose grade gliomas recur after surgery and radiotherapy. Two recent studies have reported a small number of long term survivors with this approach (Fingert & Hochberg et al., 1984;Phillips et al., 1986). The late onset of myelosuppression (usually after 10 days) when coupled with the prompt recovery produced by autologous bone marrow transplantation (usually before 20 days) would be expected to result in a relatively short period of myelosuppression even for high dose BCNU. We have explored the use of high dose BCNU (HDBCNU), 800-1,000 mg m -2 with autologous bone marrow transplantation as the primary post-surgical treatment of grade IV astrocytoma followed by full dose radiotherapy. Our hypothesis was that the high dose of the drug when given to tumours before irradiation might be expected to result in improved penetration into the tumour and an enhanced anti-tumour effect which could then be supplemented by full dose radiotherapy. Tumour volume reducti...

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“…The study was a sequential one and the regimens were exchanged and new programmes started as the lack of efficacy became apparent. HDBCNU BCNU was given at a dose of 800 mg m2 dissolved in 12 ml of alcohol solvent (Mbidde et al, 1988 Cornbleet et al (1983) and Mbidde et al (1988) respectively. The toxicity pattern of these drugs is Figure 2 a, The cumulative probability of survival for patients treated with all regimens divided according to response or non-response to chemotherapy.…”

Section: Study Methodsmentioning

confidence: 99%

Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit

Lakhani

Selby²,

Bliss³

et al. 1990

Br J Cancer

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Summary In a consecutive series of studies, 164 patients with symptomatic and/or visceral metastatic malignant melanoma were treated with single agent vindesine, high dose melphalan with autologous bone marrow transplantation (ABMT), high dose BCNU with ABMT or the BOLD (bleomycin, vincristine, CCNU and DTIC) combination. The high dose treatments and the combination chemotherapy resulted in significantly higher response rates but no prolongation of survival. Factors associated with longer survival included the absence of visceral metastases, the absence of bulky disease and good performance status. For all treatments, life

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Treatment of advanced malignant melanoma with high-dose melphalan and autologous bone marrow transplantation

Cited by 56 publications

References 10 publications

High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors

High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma

Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit

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