Phase I Trial of Radiochemotherapy with Bendamustine in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck

Bottke, Dirk; Bathe, Kathrin; Wiegel, Thomas; Hinkelbein, W.

doi:10.1007/s00066-007-1597-1

Cited by 22 publications

(13 citation statements)

References 30 publications

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“…Rosenthal et al, Dietl et al and Herrmann & Baumann described a total treatment time of < 100 days as prognostic, which was not confirmed by this study's results [6,10,26]. The question of chemotherapy application remains controversial [1,5,13,14,16]. Patients in this study had surgical approaches with adjuvant radiotherapy or primary irradiation, in both cases infrequently combined with chemotherapy.…”

Section: Discussioncontrasting

confidence: 41%

Surgery with Complete Resection Improves Survival in Radiooncologically Treated Patients with Cervical Lymph Node Metastases from Cancer of Unknown Primary

et al. 2008

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Section: Discussioncontrasting

confidence: 41%

Surgery with Complete Resection Improves Survival in Radiooncologically Treated Patients with Cervical Lymph Node Metastases from Cancer of Unknown Primary

et al. 2008

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“…Another interesting aspect of weekly cisplatin is the emerging role of trimodal therapy incorporating targeted therapies into concurrent CRT [7,8]. In an initial pilot study, Pfister et al analyzed trimodality therapy in locoregionally advanced HNSCC with cisplatin 100 mg/m 2 q21 combined with cetuximab and hyperfractionated radiotherapy [21].…”

Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy with Weekly Cisplatin 40 mg/m2 in 103 Head-and-Neck Cancer Patients

et al. 2009

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Background and Purpose:In patients with head-and-neck cancer treated with chemoradiotherapy (CRT), a cisplatin-based regimen is often used. Several treatment schedules are accepted with a cumulative cisplatin dose of 200 mg/m 2 (CisCD200) given during radiotherapy. The aim of this analysis was to investigate feasibility and efficacy of a weekly cisplatin 40 mg/m 2 regimen. Patients and Methods: During 08/2001 and 12/2006, 103 patients with squamous head-and-neck cancer received concurrent CRT with intended weekly cisplatin 40 mg/m 2 and were analyzed retrospectively. CRT was definitive for a newly diagnosed primary in 62, postoperative in 16, and for recurrence in 25 patients. Most patients had carcinoma of the hypo-and oropharynx (81%). Patients received a median total dose of 70 Gy (range, 42-71.2 Gy). Results: Only 42 patients (41%) received a CisCD200 predominantly due to hematotoxicity. Actuarial 12-and 18-month overall survival (OS) for patients with and without CisCD200 was 83.3% versus 72.1% (p = 0.19) and 66.7% versus 67.2% (p = 0.86), the 12-and 18-month locoregional control (LRC) 66.7% versus 78.7% (p = 0.325) and 59.5% versus 78.7% (p = 0.109), respectively. Multivariate analysis revealed only type of CRT (definitive vs. recurrent) and T-classification as significant variables predicting OS and LRC. Conclusion: Feasibility and efficacy of CRT with weekly cisplatin 40 mg/m 2 were suboptimal in this analysis. However, the prospects of weekly cisplatin may be its more suitable integration into emerging trimodality concepts combining CRT with molecularly targeted agents. Radiochemotherapie mit wöchentlichenCisplatingaben von 40 mg/m 2 bei 103 Patienten mit Kopf-Hals-Tumoren. Kumulative Cisplatindosis und Überleben Hintergrund und Ziel: Bei der Radiochemotherapie (CRT) von Patienten mit Kopf-Hals-Tumoren wird häufig eine platinhaltige Chemotherapie gewählt. Verschiedene Behandlungsschemata zielen auf eine kumulative Dosis von mindestens 200 mg/m 2 Cisplatin (CisCD200) simultan zur Bestrahlung. Ziel dieser Studie war es, die Wirksamkeit und Verträglichkeit wöchentlicher Cisplatingaben von 40 mg/m 2 zu untersuchen. Patienten und Methodik: Im Zeitraum von 08/2001 bis 12/2006 erhielten 103 Patienten mit Kopf-Hals-Tumoren eine CRT mit geplanten wöchentlichen Cisplatingaben von 40 mg/m 2 und wurden retrospektiv ausgewertet. 62 Patienten bekamen eine definitive CRT bei primär diagnostizierten Tumoren, 16 Patienten wurden postoperativ und 25 Patienten in einer Rezidivsituation behandelt. Hypo-oder Oropharynxkarzinome lagen in 81% (Tabelle 1) der Fälle vor. Die mediane Gesamtdosis betrug 70 Gy (Streubreite 42-71,2 Gy, Tabelle 2). Ergebnisse: Nur 42 Patienten (41%) erreichten die CisCD200 (Tabelle 3), hauptsächlich aufgrund erhöhter Hämatotoxizität. Das Gesamtüberleben (OS) nach 12 und 18 Monaten (Abbildung 1) betrug für die Patienten mit und ohne CisCD200 83,3% versus 72,1% (p = 0,19) und 66,7% versus 67,2% (p = 0,86). Die lokoregionäre Kontrolle (LRC) betrug nach 12 und 18 Monaten (Abbildung 2) 66,7% versus 78,7% ...

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“…This drug has shown therapeutic activity in a variety of tumors, including MCL and CLL, either alone or in combination with other drugs (10,12,13,22,23). Bendamustine has shown little or no accumulation in the plasma of receiver patients, thereby facilitating its lack of cross-resistance with common alkylating agents (8,24).…”

Section: Discussionmentioning

confidence: 99%

Bendamustine Is Effective in p53-Deficient B-Cell Neoplasms and Requires Oxidative Stress and Caspase-Independent Signaling

Roué¹,

López‐Guerra²,

Milpied³

et al. 2008

Clinical Cancer Research

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Purpose: Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are two incurable B-cell lymphoid neoplasms characterized by distinct clinical presentation and evolution. Bendamustine hydrochloride is a multifunctional, alkylating agent with a purine-like ring system that exhibits activity in multiple cancer models, including CLL and MCL, but whose mechanism is only partially described. Our aim was to analyze the apoptotic pathways activated by bendamustine in CLL and MCL together with the relevance of p53 mutation in determining the response to this drug. Experimental Design: Thirteen CLL/MCL cell lines and primary tumor cells from 8 MCL and 25 CLL patients were cultured for up to 24 h with bendamustine followed by cytotoxic assays, flow cytometry, immunofluorescence, and Western blot analysis of p53 response pathway and apoptosis-related factors. Results: Bendamustine displayed cytotoxic activity on most CLL and MCL primary cells and cell lines irrespective of ZAP-70 expression and p53 status. Bendamustine was found to act synergistically with nucleoside analogues in both CLL and MCL, this combination being effective in p53 mutated cases resistant to standard chemotherapy. Bendamustine cytotoxicity was mediated by the generation of reactive oxygen species and triggering of the intrinsic apoptotic pathway involving up-regulation of PUMA and NOXA, conformational activation of BAX and BAK, and cytosolic release of caspase-related and caspase-unrelated mitochondrial apoptogenic proteins. Conclusions: Our findings support the use of bendamustine as a therapeutic agent, alone or in combination, for CLL and MCL with p53 alterations and describe the molecular basis of its activity in these entities.

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Phase I Trial of Radiochemotherapy with Bendamustine in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck

Abstract: The reapplication of radiochemotherapy with bendamustine is well tolerated. The recommended dose for phase II studies was established at dose level III (bendamustine 120 mg/m(2)).

Cited by 22 publications

References 30 publications

Surgery with Complete Resection Improves Survival in Radiooncologically Treated Patients with Cervical Lymph Node Metastases from Cancer of Unknown Primary

Surgery with Complete Resection Improves Survival in Radiooncologically Treated Patients with Cervical Lymph Node Metastases from Cancer of Unknown Primary

Chemoradiotherapy with Weekly Cisplatin 40 mg/m2 in 103 Head-and-Neck Cancer Patients

Bendamustine Is Effective in p53-Deficient B-Cell Neoplasms and Requires Oxidative Stress and Caspase-Independent Signaling

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