Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation Preliminary results—Phase I study

Mr, Thomas; Robinson, William A.; Lm, Glode; Me, Dantas; Koeppler, H. F.; Morton, Nancy; Sutherland, Judy

doi:10.1097/00000421-198212000-00007

Cited by 24 publications

(5 citation statements)

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“…Few complete responders maintained a complete response longer 12 months. 67,69 This experience confirms that alkylating agents can induce responses in up to half of melanoma patients if the doses are sufficiently high. However, complete responses remain infrequent and are generally short-lived.…”

Section: Combination Chemotherapy Regimensmentioning

confidence: 64%

The History and Future of Chemotherapy for Melanoma

Yang¹,

Chapman²

2009

Hematology/Oncology Clinics of North America

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Melanoma is considered a chemotherapy-resistant tumor, but in fact several chemotherapeutic agents show single-agent activity at the level of 10% to 15%, similar to the efficacy of the chemotherapeutic armamentarium used against other tumor types. Several combination chemotherapy regimens have been tested, but no survival benefit has been demonstrated. Few of these trials have been compared with standard dacarbazine (DTIC) in an adequately powered randomized trial, and even the largest of these trials were only powered to detect unrealistically large improvements in overall survival. In this article, the authors review past chemotherapy trials and the current state of chemotherapy for melanoma. Looking to the future, the authors are encouraged by recent observations that the addition of sorafenib to DTIC (or temozolomide) can increase response rates and survival. The authors suggest that this could form the core on which additional active chemotherapeutic drugs could be added with the hope of developing a regimen that improves overall survival. This paradigm of stepwise addition of active chemotherapeutic drugs has been successful in the development of chemotherapy regimens that improve survival in other solid tumor systems. In colon carcinoma, for example, the current regimens were built on fluorouracil (5FU)/leucovorin, which has similar activity to DTIC in melanoma. This could serve as a model for studies on melanoma.

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Section: Combination Chemotherapy Regimensmentioning

confidence: 64%

The History and Future of Chemotherapy for Melanoma

Yang¹,

Chapman²

2009

Hematology/Oncology Clinics of North America

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“…There is, therefore, an urgent need to devise new approaches to the treatment of this tumour. One such approach is to use very high dose chemotherapy and preliminary work in this direction has been done by us (McElwain et al, 1979) with melphalan and by Thomas et al (1982) using nitrogen mustard, BCNU and melphalan.…”

mentioning

confidence: 99%

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

Cornbleet¹,

McElwain²,

Kumar³

et al. 1983

Br J Cancer

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Summary Twenty-eight patients with advanced life-threatening metastatic malignant melanoma were treated with high dose (140-260mgm-2) intravenous melphalan and autologous bone marrow. Cyclophosphamide "(priming" 300mgm-2 i.v. was given to 19 patients one week previously and this resulted in clinical but not histological evidence of amelioration of gastrointestinal toxicity. In 11 patients (43%) there was evidence of tumour response to treatment and in 2 patients complete remissions were observed. However in most patients, responses were short-lived and no patient lived longer than 17 months from start of treatment or 24 months from first recorded evidence of distant metastatic disease.

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“…Most previous studies using ABMT have used single courses of chemotherapy given over a short period of time. Such treatment, although likely to produce dramatic remissions, as has been previously demonstrated, is unlikely to lead to prolonged remissions and/or cure [6,15,16]. Understanding the kinetics of recovery of peripheral blood hematopoietic and bone marrow stem cells is of importance in determining timing of further therapy in the hope of obtaining more durable and prolonged remissions in such studies.…”

Section: Discussionmentioning

confidence: 97%

“…Details of the clinical aspects of these patients will be found in previous papers [6. 7], Details of the method of obtaining bone marrow for trans plantation and the techniques of preparation and infusion have been given elsewhere [6]. In brief, patients were taken to the operat ing room and 750 rnl/m2 of liquid bone marrow was aspirated into citrate phosphate dextrose bags and then stored at 10 C for 48 h before being rcinfused intravenously.…”

Section: Patient Selection and Chemotherapymentioning

confidence: 99%

Recovery of Blood and Bone Marrow Stem Cells Following Intense Chemotherapy and Autologous Bone Marrow Transplantation

Thomas¹,

Robinson²,

Mughal³

et al. 1986

Oncology

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Sixteen patients with advanced (stage III) malignant melanoma were treated with escalating doses of intravenous BCNU and melphalan starting at 400 and 35 mg/m², respectively, and escalating to 1,000 and 110 mg/m², respectively, combined with autologous marrow transplantation. The duration of granulocytopenia and time to granulocyte recovery was similar in all groups regardless of chemotherapy dose. Platelet recovery was delayed in patients receiving the highest doses of chemotherapy. This study showed that bone marrow colony-forming units in culture took as long as 6 months to recover. This was adequate to bring peripheral blood counts to normal but not to pretreatment levels. These studies indicate that autologous bone marrow transplantation is beneficial in enhancing short-term recovery, but may not be beneficial in the long-term hematopoietic recovery.

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Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation Preliminary results—Phase I study

Cited by 24 publications

References 0 publications

The History and Future of Chemotherapy for Melanoma

The History and Future of Chemotherapy for Melanoma

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

Recovery of Blood and Bone Marrow Stem Cells Following Intense Chemotherapy and Autologous Bone Marrow Transplantation

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