EORTC 24051: Unexpected side effects of a phase I study of TPF induction chemotherapy (IC) followed by chemoradiation (CRT) with lapatinib (LAP), a dual EGFR/ErbB2 inhibitor, in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (LA-LxHxSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6017-6017
Author(s):  
P. M. Specenier ◽  
Y. Lalami ◽  
J. Vermorken ◽  
D. Lacombe ◽  
I. El-Hariry ◽  
...  
Keyword(s):  
Dose Level ◽  
Renal Toxicity ◽  
Locally Advanced ◽  
Treatment Interruption ◽  
Safety Issues ◽  
Male Patients ◽  
Level 1 ◽  
Grade 3

6017 Background: CRT is considered a standard approach for LA-LxHxSCC. TPF IC regimen seems to improve outcome in locally advanced head and neck SCC. The addition of LAP was investigated in combination with a sequential therapeutic approach (IC→ CRT). Methods: Eligible tumors were SCCHN: T3-T4 larynx (Lx), T2-T4 hypopharynx (Hx) N0–3 M0. The objective of this trial is to determine MTD, DLT and recommended dose of LAP when administered with TPF IC (docetaxel (T) 75mg/m2 (60 mg/m2 for the first cycle) d1, CDDP 75mg/m2 d1, 5FU 750mg/m2/d continuous infusion d1-d5 q3weeks) followed by CRT (weekly carboplatin AUC 1.5 and RT 70Gy in 7 weeks; 2Gy/fx). LAP is administered concomitantly with IC (escalating dose 500–1500mg po daily) and during CRT (1,500 mg daily). Results: Seven male patients were included; tumor sites: LX (n = 3) / Hx: (n = 4), median age 59 years (range: 47–79), WHO PS 0–1, no severe or uncontrolled comorbidity. Three pts were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF IC). Renal toxicity was observed among these 3 pts (grade 4 [n = 1], grade 2 [n=1] and grade 1 [n=1]), with 1 DLT, leading to treatment interruption in this group. This nephrotoxicity was reversible after stopping lapatinib and hydration of the patients. As LAP plus cisplatinum plus RT was feasible in another study, a second cohort was conducted in 4 pts, receiving LAP at the same dosage, and docetaxel (T) was only introduced from cycle 2 of IC to see what is the role of T in the observed side effect. Two DLTs were observed among this second cohort of subjects: one pt presented a grade 2 renal toxicity, grade 3 diarrhea and dehydration and a second pt presented a grade 3 anorexia and grade 3 stomatitis. Based on the occurrence of 3 DLTs at the first dose level of LAP, patient recruitment was closed. Despite these safety issues, all patients recovered and were treated off-study. They will receive follow-up as foreseen by the protocol. Conclusions: These data suggest that LAP should not be combined with TPF IC regimen for LA-LxHxSCC due to prohibited toxicity. [Table: see text]

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 obatoclax mesylate in combination with bortezomib for treatment of relapsed multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8013-8013
Author(s):  
A. Keith Stewart ◽  
Suzanne Trudel ◽  
Jeffrey A. Zonder ◽  
Suzanne R. Hayman ◽  
Charles Erlichman ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
Starting Dose ◽  
Level Of Consciousness ◽  
Clinical Benefit Response ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

8013 Background: Obatoclax mesylate (GX15-070MS) is a BH3 mimetic that inhibits Bcl-2 protein family members including MCL-1, a dominant target in myeloma (MM). Obatoclax (OBX) inhibited viability of 14 MM cell lines (mean IC50 215 nM) and primary MM samples while exhibiting pre clinical synergy with bortezomib (BTZ). Sensitivity correlated with basal levels of Mcl-1 and Bcl-XL, but not Bcl2, Bim, Bax or Bak expression. Methods: We report a phase I trial of OBX in combination with BTZ. Eligibility required measureable disease, > 1 prior MM therapy, ≤10 cycles of prior BTZ and did not progress on prior BTZ therapy, creatinine ≤2 ULN. Starting dose level 1 was OBX 14 mg/m2 24-hour continuous iv. infusion days 1, 8, 15 of a 21-day cycle. BTZ given at 1.3mg/m2 iv. days 1, 4, 8 and 11. After protocol amendment OBX level 1 dosing was 30 mg/m2, level 2 was 40 mg/m2 IV both by continuous 3 hour infusion days 1, 8 and 15 on a 21 day schedule. Pre med. with famotidine was required. Results: Eleven patients were accrued, median age 62 (range: 46-77), median time from diagnosis was 4.7 years. Median of 2.5 cycles (range: 1-10). Median follow-up for patients still alive is 11.6 months (range: 0.9-35.5). At dose level 1, there were 2 DLTs. After amendment 8 patients were accrued (3 hour infusion): 4 at amended dose level 1 and 4 at dose level 2. All patients are now off treatment. 10 patients are evaluable for response: 2 patients at original dose level 1 (2 PR), 3 patients at dose level 1 (2 PR, 1 MR), no patients at dose level 2 responded: overall PR of 40%, clinical benefit response in 50% (95% CI: 19-81%). 6 patients had disease progression and 2 patients died. 4 DLTs were seen: at original dose level 1 grade 4 thrombocytopenia and delay of therapy > 15 days. At dose level 2, 1 patient had grade 3 somnolence, a 2nd patient grade 3 euphoria and grade 4 thrombocytopenia. No DLTs were seen at amended dose level 1. Common adverse events of any grade included GI, hematologic and neurologic e.g. euphoria, decreased level of consciousness, psychosis, speech. Conclusions: In summary MTD is OBX 30mg/m2 by 3 hour iv infusion once weekly, BTZ 1.3 mg/m2 days 1,4,8, and 11. Major toxicities were central neurologic and hematologic. This P2C consortium study was supported by NCI N01-CM62205.

Phase I results of the phase I/II study of pembrolizumab in combination with binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 78-78
Author(s):  
Saranya Chumsri ◽  
Mei-Yin Polley ◽  
Pulkit Mathur ◽  
Aline Reis ◽  
Kathleen S. Tenner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mapk Pathway ◽  
Locally Advanced ◽  
Level 1 ◽  
Grade 3

78 Background: Previous study demonstrated that activation of RAS/MAPK pathway is associated with reduced tumor infiltrating lymphocytes and poor response to neoadjuvant chemotherapy in triple negative breast cancer (TNBC). Further study showed that inhibition of MAPK pathway with a MEK inhibitor is synergistic with anti-PD1/PD-L1 therapies. Methods: Patients with unresectable locally advanced or metastatic TNBC with ≤ 3 prior lines of therapy without prior anti-PD-1/PD-L1/PD-L2 therapies were enrolled. Treatment was started with a 2-week run in period with single agent binimetinib. Dose level 0 was binimetinib at 45 mg oral twice daily continuously and dose level -1 was 30 mg twice daily. Pembrolizumab was given at a fixed dose of 200 mg every 3 weeks at both dose levels. Phase I study was based on the standard 3+3 design. Results: A total of 12 patients were enrolled and treated in the phase 1. Five patients were enrolled at dose level 0, 1 patient withdrew prior to treatment and 1 patient was not evaluable for dose limiting toxicity (DLT). Among 3 evaluable patients, 2 patients experienced DLT with grade 3 flank pain and ALT abnormality. Additional 8 patients were enrolled at dose level -1. Out of 6 evaluable patients for DLT, there was 1 DLT observed with grade 3 AST and ALT abnormality. However, this particular patient had liver metastasis with grade 1 AST and ALT abnormality at baseline and her liver function test (LFT) normalized in 3 weeks after treatment discontinuation and oral prednisone. Other grade 1-2 common AEs included rash, LFT increase, abdominal pain, mucositis, nausea, cardiac troponin T increase without EKG change. The efficacy data will be presented at the meeting after the phase II interim analysis. Conclusions: Pembrolizumab in combination with binimetinib at 30 mg twice daily appears to be safe based on the initial cohort. Phase II part is currently ongoing with binimetinib 30 mg twice daily and pembrolizumab 200 mg every 3 weeks with a total of 23 patients planned where the safety and efficacy of this combination will be further evaluated. Clinical trial information: NCT03106415.

scholarly journals Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1612
Author(s):  
Yeona Cho ◽  
Jun Won Kim ◽  
Ja Kyung Kim ◽  
Kwan Sik Lee ◽  
Jung Il Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Dose ◽  
Phase I ◽  
Dose Level ◽  
Dose Escalation ◽  
Level 3 ◽  
Level 1 ◽  
Grade 3 ◽  
Dose Limiting Toxicity

Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade ≥3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT.

Preliminary results of a phase I study of external beam radiation therapy (EBRT), oxaliplatin (OX), bevacizumab (BV), and capecitabine (CAP) for locally advanced or metastatic adenocarcinoma of the rectum

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3543-3543
Author(s):  
B. Czito ◽  
J. Bendell ◽  
C. Willett ◽  
G. Vaccaro ◽  
M. Morse ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Dose Level ◽  
Infusion Pump ◽  
Locally Advanced ◽  
Radiation Sensitivity ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Rectal Pain ◽  
Level 1 ◽  
Grade 3

3543 Background: BV, a monoclonal antibody against vascular endothelial growth factor, increases survival when added to first and second line chemotherapy for metastatic colorectal cancer. Preclinical studies suggest BV may enhance tumoral radiation sensitivity. Preliminary studies of OX and 5-FU based chemoradiation therapy for rectal cancer have suggested improved pathologic CR rates compared to 5-FU/ radiation alone. CAP allows fluoropyrimidine treatment without the inconvenience of an infusion pump. We investigated CAP + BV + OX + EBRT for pts with rectal cancer to evaluate for the MTD and preliminary efficacy results. Methods: Pts with adenocarcinoma of the rectum and no prior pelvic irradiation received 5040 cGy EBRT (180 cGy/fx), CAP (625–825 mg/m2 PO BID on EBRT days), BEV (15 mg/kg d1 and 10 mg/kg d8 and d22), and OX (50–75 mg/m2/week during radiation, weeks 1–5) in dose-escalating fashion. DLT was defined as any grade 3 heme tox ≥ 7d, grade 4 heme tox, grade 4 non-heme tox during chemoradiation, or inability to deliver >85% of planned treatment. Pts eligible for surgical resection could have surgery 6–8 wks after treatment completion. After recovery from surgery, patients could be treated with CAP, BV, and OX. Results: 11 patients (5 men/6 women) have been enrolled. All have completed chemoradiation and resection. At dose level 1 (CAP 625 mg/m2 BID, OX 50mg/m2) there were no DLT’s in 3 pts. 1/3 pts had G3 subarachnoid hemorrhage during adjuvant chemotherapy. At dose level 2 (CAP 825 mg/m2, OX 50 mg/m2) 2/2 pts had DLT (1 G4 diarrhea; 1 G2 rectal pain, causing treatment hold for study-defined DLT). 6 more pts were treated at dose level 1. 1pt had DLT of G3 diarrhea. G2 toxicities included diarrhea (3/11), fatigue (2/11), skin changes (2/11), and pain (2/11). 9/11 patients were downstaged. 2/11 patients had pCR at surgery and 2/11 microscopic disease only. Conclusions: CAP + BEV + OX + EBRT is a well-tolerated, active regimen for the treatment of rectal cancer. MTD was determined to be CAP 625 mg/m2 BID + BEV 15 mg/kg d1 + 10 mg/kg d 8 and 22 + OX 50 mg/m2/week. Further study of efficacy at the MTD is warranted. [Table: see text]

Feasibility study of capecitabine (cap) and cisplatin (cis) with radiation therapy (RT) in the management of patients with locally advanced unresectable squamous cell carcinoma of the head and neck (HNSCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16520-16520
Author(s):  
J. W. Allen ◽  
S. Vasireddy ◽  
J. Kaufman ◽  
J. M. Hughes ◽  
M. Sebelik ◽  
...  
Keyword(s):  
Medical Center ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Percutaneous Gastrostomy ◽  
Treatment Delays ◽  
Male Patients ◽  
Grade 3 ◽  
Dose Modifications

16520 Background: Concurrent chemoradiation has become the standard of care for locally advanced unresectable HNSCC. The most commonly used chemotherapy is cis and 5-fluorouracil (5-FU). We evaluated the feasibility of using cap and cis during RT in this population. Cap is an oral pro-drug of 5-FU that can be given daily with RT in order to enhance the activity of RT. Methods: Between Oct, 2003 and Sept, 2005, 12 male patients aged 46–83 were treated at the VA Medical Center. Patients received cis 100 mg/m2 on days 1 and 29 and cap 450 mg/m2 bid (2 hours prior to RT and 12 hours later) for 5 days of each week concurrent with RT to a total dose of 70 Gy in 35 fractions over 7 weeks. Primary endpoint of the study was toxicity. Results: All 12 patients were able to complete therapy. Treatment delays and/or dose modifications were needed in 7 patients. Treatment related toxicities included 6 patients with grade 3 mucositis and 5 patients with grade 3 dysphagia. Other grade 3 toxicities included 3 patients with dehydration and 1 patient each with leucopenia, constipation, nausea and vomiting, and odynophagia. Percutaneous gastrostomy (PEG) tubes were required in 5 patients. Complete response to chemoradiation was seen in 9 patients, 2 patients obtained partial response, and 1 patient progressed. Median progression free and overall survivals have not been reached with a median follow-up of 21 months. Conclusions: Cis and cap administered concurrently with RT has manageable toxicities and is active in patients with locally advanced unresectable HNSCC. No significant financial relationships to disclose.

Phase II trial of miniDOX (reduced-dose docetaxel/oxaliplatin/capecitabine) in “suboptimal” patients with advanced gastric cancer (AGC): TTD 08-02.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 87-87 ◽  
Author(s):  
Fernando Rivera ◽  
Bartomeu Massuti ◽  
Matilde Salcedo ◽  
Javier Sastre ◽  
Joaquina Martínez-Galán ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Efficacy Analysis ◽  
Hand Foot Syndrome ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2 ◽  
Clinical Trial Information

87 Background: Chemotherapy has improved overall survival (OS) in patients (p) with AGC and docetaxel (D), oxaliplatin (O) and capecitabine (X), have shown consistent activity in this setting. We defined "Suboptimal" p as those with PS ECOG-2 and/or weight loss 10-25% and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. Methods: We explored in 43 previously untreated "suboptimal" AGC p the "miniDOX" regimen (D: 40 mg/m2 iv, d1; O: 80 mg/m2 iv d1; C: 625 mg/m2 po bid, d1 to 21, every 21d; after 6 courses only C was maintained). D and O dose were allowed to be increased to 45 and 90 mg/m2 respectively (dose level +1) and to 50 and 100 mg/m2 (level +2) if less than grade 2 toxicity after the first 2 courses. One p that did not received any dose of chemotherapy, was included in the ITT efficacy analysis but not in the safety analysis. Primary endpoint was Response Rate (RR), Toxicity, Progression Free Survival (PFS) and OS were secondary objectives. Results: p characteristics: PS ECOG-2:12 p, Weigh loss 10-25%:23 p; median age 73.3 years (40-87); 32 males; locally advanced:8 p/metastatic:35 p; Primary site:Gastric 32 p/ EGJ 11; In 19 p the dose of D and O were increased to level +1 and in 8 of them to level +2. Worst toxicity per p (Grade 3-4): neutropenia: 5 p (3 of them with febrile neutropenia); pulmonary embolism (PE):4 p (3 of them suffered sudden death and the PE was suspected but not confirmed); diarrhea:9 p; paronychia:2 p; CVA:1 p; renal failure:1 p (this p suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome:4 p and asthenia:5 p. Response: CR:1 p, PR:23 p (RR: 56%), SD:12 p, Progression:3 p, No determined:4 p; With a median follow-up of 27 months, 36 p have died (toxicity:4 p, progressive disease:32 p). Median and 1 year actuarial PFS and OS are 5.5 months/19% and 13.3 months/54% respectively. Conclusions: Although relevant the toxicity of miniDOX has been found, its activity is encouraging in "suboptimal" pts with AGC and this combination should be further investigated in this setting. Clinical trial information: NCT00733616.

scholarly journals Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuhei Miyasaka ◽  
Hidemasa Kawamura ◽  
Hiro Sato ◽  
Nobuteru Kubo ◽  
Tatsuji Mizukami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Therapeutic Benefit ◽  
Carbon Ion Radiotherapy ◽  
Safety And Efficacy ◽  
Carbon Ion ◽  
Grade 3 ◽  
Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

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