Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients.

Robins, H. Ian; Cohen, Justin D.; Schmitt, C. L.; Tutsch, Kendra D.; Feierabend, Chris; Arzoomanian, Rhoda Z.; Alberti, Dona; d'Oleire, F; Longo, Walter L.; Heiss, C

doi:10.1200/jco.1993.11.9.1787

Cited by 62 publications

(53 citation statements)

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“…In this trial, WBH was induced extracorporeally using a hemodialysis device. As was the case in the earlier carboplatin trial [14], white blood cell and platelet nadirs were not affected by the addition of WBH. Interestingly, responses were observed in 3 of 12 (25%) refractory sarcoma patients in this (mixed histology) pilot study.…”

Section: Systemic Ht: Looking Back Moving Forwardsupporting

confidence: 48%

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Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Feyerabend¹,

Wiedemann²,

Richter³

et al. 1999

Oncol Res Treat

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Laboratory and clinical data confirm that hyperthermia may enhance the therapeutic index of ionizing radiation and specific cytotoxic drugs. As for whole-body hyperthermia (WBH), several generations of trials have been performed. Especially in refractory sarcomas, the combination of WBH and chemotherapy with ifosfamide, carboplatin, and etoposide led to a striking increase of response rates compared to chemotherapy alone. Toxicity of WBH procedures can be limited by using a radiant heat device. To evaluate the role of WBH in different tumor entities, several trials are under way. Hyperthermia, especially WBH, seems to stimulate the immune system, e. g. natural killer cell activity and number of cytotoxic T cells. Furthermore, the expression of the intracellular adhesion molecule 1 in tumors is enhanced by WBH, leading to an increased response of lymphokine-activated killer cells. As for locoregional hyperthermia, local control rates can be increased in combination with radiotherapy, e. g. in recurrent breast cancer and melanoma. Triple modality therapy (radiochemo-thermotherapy) seems to be useful especially in large lesions with poor prognosis.

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Section: Systemic Ht: Looking Back Moving Forwardsupporting

confidence: 48%

“…Based on preclinical studies, Robins et al [14] conducted a phase I study of 41.8°C WBH and carboplatin. The experimental design allowed for the comparison of the effects of WBH alone to carboplatin alone, and to the combination of WBH combined with carboplatin for each patient.…”

Section: Systemic Ht: Looking Back Moving Forwardmentioning

confidence: 99%

Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Feyerabend¹,

Wiedemann²,

Richter³

et al. 1999

Oncol Res Treat

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“…Nowadays, with locoregional hyperthermia it is possible to reach a temperature of 41~ (Overgaard et al 1995;van Dijk et al 1990), while whole-body hyperthermia is capable of inducing 41.8~ (Robins et al 1993). The combination of locoregional hyperthermia with cisplatin (Rietbroek et al 1995(Rietbroek et al , 1996 or ifosfamide (Issels et al 1990) has proven to be feasible and has given promising response rates.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of locoregional hyperthermia with cisplatin (Rietbroek et al 1995(Rietbroek et al , 1996 or ifosfamide (Issels et al 1990) has proven to be feasible and has given promising response rates. The combination of whole-body hyperthermia and carboplatin at 41.8~ was also feasible, with ongoing multicentre studies (Robins et al 1993). Cisplatin cannot be used at a systemic temperature of 41.8~ because of severe renal toxicity (Gerad et al 1983;Mella et al 1987).…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

Rietbroek

Vaart

Haveman

et al. 1997

J Cancer Res Clin Oncol

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Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract The cytotoxicity of cisplatin and cisplatin-DNA adduct formation in vitro and in vivo is clearly enhanced by hyperthermia. We investigated whether cytotoxicity and platinum-DNA adduct formation of two promising new third-generation platinum derivatives, lobaplatin [1,2-diamminomethylcyclobutane platinum(II) lactate] and oxaliplatin [oxalato-l,2-diaminocyclohexane platinum(II)], are also enhanced by hyperthermia. Cisplatin was used for comparison. SW 1573 cells were incubated with cisplatin, lobaplatin or oxaliplatin at different concentrations for 1 h at 37 ~ 41 ~ and 43~ The reproductive capacity of cells was determined by cloning experiments. Immunocytochemical detection of platinum-DNA adducts was performed with the rabbit antiserum NKI-A59. At 37~ cisplatin was the most cytotoxic, followed by oxaliplatin and lobaplatin. Hyperthermia clearly enhanced the cytotoxicity of cisplatin, lobaplatin and oxaliplatin. There was no further increase in cytotoxicity at 43~ compared to 41~ for cisplatin and oxaliplatin. A further increase in cytotoxicity at 43~ was observed for lobaplatin. At 43~ thermal enhancement was higher for lobaplatin than for oxaliplatin, with the reverse pattern at 41~ For both drugs, thermal enhancement of cytotoxicity was lower than observed for cisplatin. Immunocytochemical detection of platinum-DNA adducts was feasible for all the drugs. Adduct formation was enhanced at 43~ for cisplatin, lobaplatin and oxaliplatin with a relative increase of 410%, 170% and 180%. These results seem to confirm that an increase in platinum-DNA adduct formation is involved in the in vitro thermal enhancement of cytotoxicity. The observed thermal enhancement of cytotoxicity of lobaplatin and oxaliplatin in vitro warrants further in vivo investigations.

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“…A series of laboratory studies on carboplatin cytotoxicity and hyperthermia [14, 15, 16, 19, 20, 22]resulted in Robins et al [31]conducting a phase I study of WBH and carboplatin (CBDCA). The experimental design of this clinical trial allowed for the comparison of the effects of WBH alone to CBDCA alone and to the combination of WBH and CBDCA for each patient.…”

Section: Introductionmentioning

confidence: 99%

A Systemic Hyperthermia Oncologic Working Group Trial

et al. 2003

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Background: Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8°C (×60 min) radiant heat (Aquatherm^®) whole-body hyperthermia (WBH) with ‘ICE’ chemotherapy. The ICE regimen consists of ifosfamide (5 g/m²), carboplatin (300 mg/m²) and etoposide (100 mg/m²), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH. Methods: Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim. Results: Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status ∼1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction. Conclusion: These results are consistent with continued clinical investigation of this combined modality approach.

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Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients.

Abstract: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.

Cited by 62 publications

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Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

A Systemic Hyperthermia Oncologic Working Group Trial

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