febrile neutropenia/hypoxia

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The Diagnostic Utility and Clinical Implications of Bronchoalveolar Lavage in Cancer Patients With Febrile Neutropenia and Lung Infiltrates

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Introduction Febrile neutropenia (FN) is a dreaded complication of cancer chemotherapy and frequently associated with respiratory infections. Flexible bronchoscopy (FB) serves as a useful diagnostic tool in this regard. Objective To determine the diagnostic yield, safety and clinical implications of

Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia.

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We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and

A phase I trial of PR-104, a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumors.

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OBJECTIVE PR-104 is a "pre-prodrug" designed to be activated to a dinitrobenzamide nitrogen mustard cytotoxin by nitroreduction in hypoxic regions of tumors. This study was conducted to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and pharmacokinetics (PK) of

A phase I combination study of olaparib with cisplatin and gemcitabine in adults with solid tumors.

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OBJECTIVE To determine the safety and tolerability of olaparib with cisplatin and gemcitabine, establish the maximum tolerated dose (MTD), and evaluate the pharmacodynamic and pharmacokinetic profile of the combination. METHODS We conducted a phase I study of olaparib with cisplatin and gemcitabine

Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study.

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Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia. Improving outcomes by targeting mechanisms of drug resistance is a potential solution.We report results investigating the epigenetic modulators

Transient hypoxaemia during neutrophil recovery in febrile patients.

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In previous anecdotal reports, treatment with granulocyte colony-stimulating factor has been associated with pulmonary toxicity. In 35 consecutive admissions for chemotherapy-induced febrile neutropenia, transient hypoxia occurred in 12. 10 of the 12 followed treatment with filgrastim to induce

Evaluation of adverse events associated with filgrastim originator and biosimilar using a spontaneous reporting system database.

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Biosimilar products of filgrastim have become available for improved sustainability of cancer care; however, the real-world safety profile remains unknown. The purpose of this study was to clarify the adverse events associated with filgrastim originator and its biosimilar using the Japanese Adverse

Tirapazamine plus carboplatin and paclitaxel in advanced malignant solid tumors: a california cancer consortium phase I and molecular correlative study.

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OBJECTIVE Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells and has supra-additive toxicity with platinums and taxanes in preclinical studies. We conducted a Phase I study of tirapazamine, carboplatin, and paclitaxel and assessed

A phase 2 study of ATRA, arsenic trioxide, and gemtuzumab ozogamicin in patients with high-risk APL (SWOG 0535).

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High-risk acute promyelocytic leukemia (APL) remains a therapeutic challenge, with higher associated rates of early mortality and relapse than standard-risk APL. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) is a well-established treatment for patients with standard-risk APL, but it is

Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer.

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OBJECTIVE The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). METHODS Treatment began with two cycles of topotecan (1 mg/m(2)) Days 1

PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma.

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OBJECTIVE PR-104 is activated by reductases under hypoxia or by aldo-keto reductase 1C3 (AKR1C3) to form cytotoxic nitrogen mustards. Hepatocellular carcinoma (HCC) displays extensive hypoxia and expresses AKR1C3. This study evaluated the safety and efficacy of PR-104 plus sorafenib in

Phase II study of tirapazamine, cisplatin, and etoposide and concurrent thoracic radiotherapy for limited-stage small-cell lung cancer: SWOG 0222.

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OBJECTIVE A SWOG pilot study (S0004) showed that tirapazamine (TPZ) when combined with concurrent chemoradiotherapy yielded a promising median survival of 22 months in limited-stage small-cell lung cancer (LSCLC). We report results of the phase II study designed to confirm this result. METHODS The

Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003.

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OBJECTIVE Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment

A phase I and pharmacokinetic study of oral 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in the treatment of advanced-stage solid cancers: a California Cancer Consortium Study.

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BACKGROUND 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a novel small-molecule ribonucleotide reductase inhibitor. This study was designed to estimate the maximum tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced-stage solid tumors. METHODS Twenty

Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer.

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OBJECTIVE To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. METHODS The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant

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