A phase I study of tirapazamine in combination with radiation and weekly cisplatin in patients with locally advanced cervical cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5543-5543
Author(s):  
D. Rischin ◽  
K. Narayan ◽  
A. Oza ◽  
L. Mileshkin ◽  
D. Bernshaw ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Pulmonary Embolism ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Level 1 ◽  
Grade 3

5543 Background and Purpose: Hypoxia is an adverse prognostic factor in locoregionally advanced cervical cancer treated with radiation. GOG are currently studying the hypoxic cytotoxin, tirapazamine (TPZ) in combination with biweekly intermediate dose cisplatin (CIS) and radiation in a large phase III trial. The aim of this phase I study was to develop a better tolerated regimen that added TPZ to the standard regimen of radiation and weekly low dose CIS. Methods: Eligible patients had previously untreated carcinoma of the cervix, Stages IB2 - IVA. The starting schedule was radiotherapy (45 to 50.4 Gy external beam radiation followed by brachytherapy), with concomitant weekly CIS 40 mg/m2 weeks 1–6 and weekly TPZ 290 mg/m2 (prior to CIS) in weeks 1–5. Results: Between 3/05 and 7/06 eleven patients were enrolled, median age (range) 52 (31–65), squamous cell carcinoma 10, adenocarcinoma 1, 1B2–5, IIA-1, IIB-3, IIIB- 1, IVA-1. The first 2 patients on dose level 1 experienced a dose limiting toxicity (DLT), one grade 3 ALT (SGPT) elevation and grade 4 pulmonary embolism and one grade 3 ototoxicity. Doses were decreased to dose level -1 CIS 30 mg/m2 and TPZ 260 mg/m2. Three patients were treated without any DLTs. Six patients were then treated on dose level -1a, CIS 35 mg/m2 and TPZ 260 mg/m2, with 2 DLTs: grade 3 neutropenia with dose omission and grade 4 pulmonary embolism with major hemodynamic compromise. The sixth patient on dose level -1a withdrew from the trial in week 2 after being advised about the DLTs observed on this dose level. 3 additional patients will be accrued on dose level -1 to confirm safety of this dose level. One patient has relapsed in pelvic nodes, all other patients remain disease-free with a median followup of 10 months (range 5 - 21) Conclusions: The combination of weekly TPZ and CIS with radiation for locally advanced cervical cancer was associated with more toxicity than anticipated with the recommended dose level being TPZ 260 mg/m2, CIS 30 mg/m2. No significant financial relationships to disclose.

Phase 1 Study of Tirapazamine in Combination With Radiation and Weekly Cisplatin in Patients With Locally Advanced Cervical Cancer

2010 ◽  
Vol 20 (5) ◽  
pp. 827-833 ◽  
Author(s):  
Danny Rischin ◽  
Kailash Narayan ◽  
Amit M. Oza ◽  
Linda Mileshkin ◽  
David Bernshaw ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Pulmonary Embolism ◽  
Dose Level ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Level 1 ◽  
Grade 3 ◽  
Experienced Grade

Introduction:Hypoxia is an adverse prognostic factor in locoregionally advanced cervical cancer treated with radiation. The aim of this phase I study was to develop a well-tolerated regimen that added tirapazamine to the standard regimen of radiation and weekly low-dose cisplatin.Methods:Eligible patients had previously untreated carcinoma of the cervix, stages IB2 to IVA. The starting schedule was radiotherapy (45-50.4 Gy external beam radiation followed by brachytherapy), with concomitant weekly intravenous cisplatin, 40 mg/m2 on weeks 1 to 6 and weekly intravenous tirapazamine, 290 mg/m2 in weeks 1 to 5.Results:Eleven patients were enrolled. The median age was 52 years (range, 31-65 years). Ten patients had squamous cell carcinoma and 1 patient had adenocarcinoma; 5 patients had stage 1B2 disease, 1 had stage IIA, 3 had stage IIB-3, 1 had stage IIIB, and 1 had stage IVA. The first 2 patients on dose level 1 experienced a dose-limiting toxicity (DLT): 1 experienced grade 3 alanine amino transferase elevation and grade 4 pulmonary embolism, and 1 experienced grade 3 ototoxicity. Doses were decreased to dose level −1 with a 30-mg/m2 dose of cisplatin and a 260-mg/m2 dose of tirapazamine. Three patients were treated without any DLTs. Six patients were then treated on dose level −1a: a 35-mg/m2 dose of cisplatin and a 260-mg/m2 doses of tirapazamine with 2 DLTs-grade 3 neutropenia with dose omission and grade 4 pulmonary embolism with major hemodynamic compromise. Three of 10 evaluable patients have experienced locoregional failure.Conclusions:The combination of weekly tirapazamine and cisplatin with radiation for locally advanced cervical cancer was associated with more toxicity than anticipated with the recommended dose level being tirapazamine 260 mg/m2 and cisplatin 30 mg/m2. Further study of this weekly schedule is not warranted.

A phase I study of docetaxel as a radiosensitizer for locally advanced squamous cell cervical cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5053-5053
Author(s):  
E. A. Alvarez ◽  
A. H. Wolfson ◽  
J. M. Pearson ◽  
M. Crisp ◽  
N. C. Lambrou ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Study ◽  
Locally Advanced ◽  
Concurrent Radiotherapy ◽  
Level 1 ◽  
Experienced Grade

5053 Background: Concomitant radiotherapy with cisplatin chemotherapy is the standard of care for locally advanced squamous cell cervical cancer (LASCCC). Alternatives to cisplatin are needed due to patient intolerance or toxicity. Taxanes have demonstrated clinical cytotoxic activity to SCCC and in-vitro radio-sensitization. This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy for the primary treatment of LASCCC. Methods: Twenty-three patients with FIGO stage IIB-IVA LASCCC without para-aortic lymph node involvement were screened and 13 enrolled in a dose-escalating phase I study. Docetaxel dose levels were 20 mg/m2, 30 mg/m2 and 40 mg/m2 given intravenously every 7 days for 6 cycles. Three patients were treated at each dose level and six patients received the MTD. Radiation therapy (RT) delivered a total dose of approximately 85 Gy to Point “A”. RT was administered with megavoltage external beam irradiation (EBI) at 1.8 Gy/fraction (fx) for 30 fxs to the pelvis over 6 weeks using a 4-field “box” technique for the first 25 fxs. A midline shield was applied for the last 5 fxs. Following EBI, patients underwent low-dose-rate brachytherapy. Results: Thirteen patients completed 4 - 6 cycles of chemotherapy. The other patients withdrew consent or needed alternative treatment before initiating the study. Reasons for completing less than 6 cycles were: noncompliance (5), adverse event (2), progression (1). One patient was lost to follow-up after 4 cycles. DLT’s were not observed at the 20 mg/m2 dose level. At the 30 mg/m2 dose level, 1/4 patient had a treatment-unrelated pelvic abscess and celiotomy. Another had progression 4 months after treatment. At the 40 mg/m2 dose level, 1/6 patients had progression and experienced grade 2 pneumonia, not treatment related. DLT was not observed in 6 patients at the 40 mg/m2 level. Overall, 5/13 (38%) experienced grade 2 diarrhea, 5 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. Seven of 9 patients (78%) had no evidence of disease with follow-up ranging from 10–21 months. Conclusions: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for LASCCC is 40 mg/m2. The phase II trial is underway. No significant financial relationships to disclose.

Phase I trial of nelfinavir added to cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer

2019 ◽  
Vol 154 ◽  
pp. 267-268 ◽  
Author(s):  
A.E. Garcia-Soto ◽  
N.D. McKenzie ◽  
J.M. Pearson ◽  
L. Portelance ◽  
J.A. Lucci ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Advanced Cervical Cancer ◽  
Pelvic Radiation ◽  
Locally Advanced Cervical Cancer

Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 139-139
Author(s):  
H. Ishigami ◽  
J. Kitayama ◽  
S. Kaisaki ◽  
H. Yamaguchi ◽  
H. Yamashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Dose Level ◽  
Peritoneal Metastasis ◽  
Phase I Study ◽  
Level 1 ◽  
Grade 3 ◽  
Gastric Cancer Patients ◽  
Experienced Grade

139 Background: Intraperitoneal (IP) chemotherapy is promising for the treatment of gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous (IV) PTX in phase I and phase II studies (Oncology. 2009; Ann Oncol. 2010). Secondly, we developed a new IP-containing chemotherapy regimen, IV PTX plus IP cisplatin (CDDP) and PTX, for patients who have failed S-1-based chemotherapy. We performed a phase I study to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Methods: A total of 9 gastric cancer patients were enrolled who had shown progression of peritoneal metastasis after S-1-based chemotherapy. PTX was administered intravenously at a dose of 100 mg/m2 and intraperitoneally over 1 hour with an initial dose of 20 mg/m2 (level 1), stepped up to 30 or 40 mg/m2 depending on observed toxicity. CDDP was subsequently administered intraperitoneally at a dose of 30 mg/m2 over 24 hours after PTX infusion. PTX and CDDP were administered on days 1 and 15 in 4-week cycles. Results: At dose level 1, dose-limiting toxicities (DLTs) were observed in 2 of 3 patients. One patient experienced grade 4 leukopenia, and the other grade 3 vomiting. Because of higher toxicities than anticipated, the initial dose-escalation schedule was abandoned, and the doses of IV PTX and IP CDDP were reduced to 80 mg/m2 and 25 mg/m2, respectively, while keeping the dose of IP PTX at 20 mg/m2 (level 0). At dose level 0, one of the first 3 patients experienced grade 3 nausea, and an additional 3 patients experienced no DLTs. Consequently, the MTD and RD were determined to be dose level 1 and dose level 0, respectively. No patients experienced complications related to the peritoneal access device or IP infusion. Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials. No significant financial relationships to disclose.

scholarly journals Concurrent Definitive Chemoradiation Incorporating Intensity-Modulated Radiotherapy Followed by Adjuvant Chemotherapy in High Risk Locally Advanced Cervical Squamous Cancer: A Phase Ⅱ Study.

2021 ◽  
Author(s):  
Gong-yi ZHANG ◽  
ZHANG Rong ◽  
Ping BAI ◽  
Shu-min LI ◽  
Yuan-yuan ZHANG ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Intensity Modulated Radiotherapy ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer ◽  
Intensity Modulated ◽  
Grade 3

Abstract Background Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage ⅢB-ⅣA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseⅡ study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. Objectives to determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. Study Design: Patients were enrolled if they had biopsy proven stage ⅢA-ⅣA squamous cervical cancer or stage ⅡB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0Gy at 1.8Gy ~ 2.0Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0–65 Gy at 2.0- 2.6Gy/fraction in 25 fractions. A total dose of 28 ~ 35Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30mg/m2 was initiated on the first day of radiotherapy for over 1-hour during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-hour infusion on day1, followed by cisplatin 35 mg/m2 with 1-hour infusion on day1-2 (70 mg/m2 in total). Results Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4 ,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3–4 leukopenia and thrombocytopenia, respectively. Grade 3–4 late toxicities were reported in 3 patients. Conclusions The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

Sign in / Sign up

Export Citation Format

Share Document