A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies

Forouzannia, Afshin; Schiller, Joan H.; Berlin, Jordan; Hutson, Paul R.; Boothman, David A.; Storer, Barry; Wilding, George; Mehta, Minesh P.

doi:10.1016/j.lungcan.2003.10.005

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…Furthermore, it is important that the drug concentrations shown to enhance the growth delay induced by 131 I‐MIP‐1095 are clinically relevant. It has been shown that the radiosensitising concentrations of DSF:Cu, olaparib, topotecan and bortezomib described in this report are achievable in the plasma of patients (Table ) . Currently, there is no phase I or II clinical trials involving nutlin‐3…”

Section: Discussionmentioning

confidence: 82%

“…It has been shown that the radiosensitising concentrations of DSF:Cu, olaparib, topotecan and bortezomib described in this report are achievable in the plasma of patients ( Table 2). [19][20][21][22][23][24][25][26] Currently, there is no phase I or II clinical trials involving nutlin-3. [27,28] While it is expected that the most significant influence of treatment with radiosensitisers will be potentiation of the damage inflicted by decay particle bombardment of susceptible cellular elements, it is noteworthy that enhancement of therapeutic efficacy of radiopharmaceutical may also result from increased cellular uptake.…”

Section: Discussionmentioning

confidence: 99%

“…Based on these results, a radioactivity concentration of 0.37 MBq/ml 131 I-MIP-1095 was selected for the assessment of the modulation of radiopharmaceutical-induced growth delay. [20] 24.8-108.9 nM [25] Olaparib 1 lM 0.23-2.3 lM [24] 5.75 lM [23] 11 lM [24] Bortezomib 10 nM 580 nM [21] 205.60 nM [22] 14.53 0.65 *** 5.62 0.24 *** 0.37 MBq/ml…”

Section: Morphological Characterisation Of Lncap Spheroidsmentioning

confidence: 99%

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Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs

Tesson

Rae

Nixon

et al. 2016

Journal of Pharmacy and Pharmacology

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ObjectivesDespite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. 131I‐MIP‐1095 is a recently developed prostate‐specific membrane antigen (PSMA)‐targeting, small molecular weight radiopharmaceutical which has anti‐tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining 131I‐MIP‐1095 with cytotoxic drug treatments.MethodsVarious cytotoxic agents were evaluated in combination with 131I‐MIP‐1095 for their capacity to delay the growth of LNCaP cells cultured as multicellular tumour spheroids. Two end‐points were used to assess treatment efficacy: (i) the time required for doubling of spheroid volume and (ii) the area under the volume–time growth curves.Key findingsThe PARP‐1 inhibitor olaparib, the topoisomerase I inhibitor topotecan, the proteasome inhibitor bortezomib, the inhibitor of the P53–MDM2 interaction nutlin‐3 and the copper‐chelated form of the oxidising agent disulfiram (DSF:Cu) all significantly enhanced the inhibition of the growth of spheroids induced by 131I‐MIP‐1095. However, the Chk1 inhibitor AZD7762 failed to potentiate the effect of 131I‐MIP‐1095.ConclusionsThese results indicate that targeted radiotherapy of prostate cancer may be optimised by combining its administration with chemotherapy.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Morphological Characterisation Of Lncap Spheroidsmentioning

confidence: 99%

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Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs

Tesson

Rae

Nixon

et al. 2016

Journal of Pharmacy and Pharmacology

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“…Like cisplatin, topotecan is a potent radiosensitizer in clinically feasible doses as low as 2–10 μM in vitro (25) or 20 mg/kg in vivo (24) . Phase I and II studies in various types of tumors, especially non–small‐cell lung cancer, have demonstrated the drug to be safe within the range 0.4–0.5 mg/m 2 /week when used concurrently with radiation (26–28) .…”

Section: Topotecan and Concurrent Radiationmentioning

confidence: 99%

Topotecan in cervical cancer

Ackermann

Beckmann

Thiel

et al. 2007

Int J Gynecol Cancer

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Recurrent and advanced cervical cancers are associated with high mortality and a lack of effective treatment options, especially for women who are poor candidates for surgery or radiation therapy. The broad clinical effectiveness and manageable toxicity of topotecan in other human malignancies as well as promising recent study results suggest that it is highly effective in treating cervical tumors. We therefore conducted a systematic review on the studies using topotecan in cervical cancer. Seven phase I-III clinical trials using topotecan, both as a single agent and in combination with cisplatin or paclitaxel, in patients with recurrent or advanced carcinoma of the cervix were reviewed. Data from two studies in which topotecan was used in combination with radiotherapy for induction therapy were also evaluated. Although single-agent cisplatin-based chemoradiotherapy is the standard of care for high-risk or locally advanced cervical cancer, topotecan, when used concurrently with cisplatin and/or radiation therapy, produces high objective response rates and prolonged survival. Gynecologic Oncology Group (GOG) Protocol 179 for the first time showed significantly improved overall survival and progression-free survival in a combination therapy for advanced cervical cancer compared to cisplatin alone. Recent data suggest that topotecan, when used concurrently with cisplatin, may be the new standard of care for the management of recurrent or advanced cervical cancer. Ongoing phase III studies (GOG-204, AGO-Zervix-1) will compare this combination with other cisplatin-containing and cisplatin-free combinations. Moreover, further evaluation of topotecan appears to be warranted in conjunction with radiotherapy and in the neoadjuvant setting as well as in combination with novel biologic agents.

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Current experience with mIBG therapy in combination with chemotherapy and radiosensitizers

Gaze

Fersht

2008

Nuclear Medicine and Biology

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A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies

Cited by 6 publications

References 15 publications

Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs

Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs

Topotecan in cervical cancer

Current experience with mIBG therapy in combination with chemotherapy and radiosensitizers

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