scholarly journals Clinical analysis of conformal and intensity-modulated radiotherapy in patients with recurrent ovarian cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hua Yang ◽  
Kaishuo Zhang ◽  
Zi Liu ◽  
Tao Wang ◽  
Fan Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Recurrent Ovarian Cancer ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Intensity Modulated ◽  
Gi Toxicity ◽  
Grade 3 ◽  
Radiotherapy Dose ◽  
3D Crt

Abstract We aimed to provide evidence for radiotherapy treatment regimens in patients with clinically recurrent ovarian cancer. We analyzed the survival and prognostic factors in 43 patients who were treated for recurrent ovarian cancer at 58 tumor sites using three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) during January 2006–December 2017. t years 1, 2, and 3, overall survival (OS) rate was 82.4%, 68.4%, and 57.9%; local control (LC) rate was 100%, 100% and 80%; recurrence free survival (RFS) rate was 86.8%, 66.6%, and 61.1%; and disease-free survival (DFS) rate was 79.7%, 56.7%, and 46.8%, respectively. The radiotherapy technique was determined to be an independent prognostic factor for survival; the survival rate of patients was significantly improved with IMRT compared to 3D-CRT (P = 0.035). Radiotherapy dose was an independent prognostic factor; survival rate improved when patients were treated with a radiation dose ≥ 60 Gy as compared to < 60 Gy (P = 0.046). Elective nodal prophylactic radiation therapy (ENRT) did not lead to a significant improvement in survival when compared to involved-field radiation therapy (IFRT). The toxicities of 3D-CRT and IMRT were tolerable. One patient (2.3%) had grade 3 acute gastrointestinal (GI) toxicity, 2 (4.6%) grade 3 late GI toxicity, 5 (11.6%) grade 3 hematological toxicity, and 2 (4.6%) had grade 4 hematological toxicity. IMRT improved LC and OS in patients with recurrent ovarian cancer after surgery and multiple chemotherapy; toxicities were tolerable. The IMRT technique and radiotherapy dose of ≥ 60 Gy had independent prognostic significance for the survival of such patients.

Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial

2021 ◽  
pp. JCO.20.02530
Author(s):  
Supriya Chopra ◽  
Sudeep Gupta ◽  
Sadhana Kannan ◽  
Tapas Dora ◽  
Reena Engineer ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Late Toxicity ◽  
Free Survival ◽  
Image Guided ◽  
Intensity Modulated ◽  
Gi Toxicity ◽  
Disease Free ◽  
Pelvic Relapse ◽  
3D Crt

PURPOSE Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea ( P = .04), improved appetite ( P = .008), and lesser bowel symptoms ( P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION IG-IMRT results in reduced toxicity with no difference in disease outcomes.

scholarly journals Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma

2016 ◽  
Vol 58 (3) ◽  
pp. 351-356 ◽  
Author(s):  
Katsuya Yahara ◽  
Takayuki Ohguri ◽  
Hiroki Udono ◽  
Junkoh Yamamoto ◽  
Kyosuke Tomura ◽  
...  
Keyword(s):  
Hyperbaric Oxygen ◽  
Tumor Volume ◽  
Combined Therapy ◽  
Survival Rates ◽  
Intensity Modulated Radiotherapy ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Promising Treatment ◽  
Grade 3

Abstract The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1.5–2.0 cm. The IMRT boost doses were then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO to achieve radiosensitization. The planned RT dose was completed in all patients, while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain. The toxicities were mild, no non-hematological toxicity of Grade 3–5 was observed. The 2-year overall survival (OS) and progression-free survival rates in all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1 months. In conclusion, the combined therapy of RT using IMRT boosts after HBO with chemotherapy was a feasible and promising treatment modality for patients with glioblastoma. The results justify further evaluation to clarify the benefits of this therapy.

A phase I study of modified irinotecan (CPT-11) plus cisplatin (CDDP) [m-IP] against paclitaxel/carboplatin [TC] -resistant and recurrent ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13015-13015
Author(s):  
T. Suzuki ◽  
M. Morishita ◽  
M. Matsuura ◽  
T. Fujimoto ◽  
R. Tanaka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Hematological Toxicity ◽  
Prior Chemotherapy ◽  
Level 3 ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

13015 Background: CPT-11/CDDP is effective regimen for ovarian cancer. Particularly against ovarian cancer resistant to prior chemotherapy, a 40% response rate was reported (Sugiyama T Cancer Letters, 1998). However, every 4 weeks treatment with CPT-11 day 1, 8, and 15, administration on day 15 was skipped in about 60% due to toxicity, and the relative dose intensity of IP was 66.7% in non-small cell lung cancer (Saito H Am J Clin Oncol 2006). We planed Phase I study, in consideration of the effect of prior chemotherapy in TC-resistant ovarian cancer, a modified CPT-11 (day 1, 8) and CDDP (day 1) for every 4 weeks treatment (m-IP). The aim of this study conducted to examine the dose limiting toxicity (DLT), to evaluate the maximum tolerated dose (MTD), and define the recommended dose (RD) for a phase II study. Methods: Patients with TC-resistant ovarian cancer having a PS 0–1, age 30–75 years, normal organ functions, and written informed consent. CPT-11 was administered intravenously over 90 minutes on day 1 and day 8, plus CDDP was day 1, repeated every 4 weeks. The dose escalation schedule was defined: Doses of CPT-11/CDDP (mg/m2) were 60/60 at level 1, 70/60 at level 2 and 70/70 at level 3. DLT were determined as Grade 4 hematological toxicity and = Grade 3 non-hematological toxicity occurred, and when dosing on day 8 was delayed for more than 8 days due to toxicity. Results: Nine patients were enrolled (level 1/2/3: 3/3/3). DLTs, at level 1 and 2, no patients developed. At level 3, grade 3 nausea and vomiting and delayed treatment on day 8 due to anorexia, were observed in all of 3 patients. Therefore, MTD was determined to be level 3 and RD was determined to be level 2 (CPT-11: 70mg/m2, CDDP: 60mg/m2). Major =Grade 3 toxicities observed were leukopenia, neutropenia, nausea, and vomiting. No Grade 4 hematological toxicities were observed. Diarrhea was mild. Antitumor effect at RD was observed in 1 patient with CR, 1 patient with PR and 1 patient with PD. Conclusions: The MTD of m-IP was CPT-11 70mg/m2 and CDDP 70mg/m2 (level 3), the RD was CPT-11 70mg/m2 and CDDP 60mg/m2 (level 2). Preliminary response are promissing associated with tolerable toxicity for TC-resistant and recurrent ovarian cancer. A Phase II study is currently conducted. 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.

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: An open-label single-arm, phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6023-6023
Author(s):  
Mingyuan Chen ◽  
Yijun Hua ◽  
Rui You ◽  
Zhi-Qiang Wang ◽  
Peiyu Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Intensity Modulated Radiotherapy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Intensity Modulated ◽  
Local Surgery ◽  
Recurrent Nasopharyngeal Carcinoma ◽  
Grade 3

6023 Background: Toripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 (PD-1). We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC). Methods: We conducted a single-arm, phase II trial with rNPC patients who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate (ORR). The secondary endpoints included safety profiles, progression-free survival (PFS). Results: Between May 2019 and January 2020, a total of 25 rNPC patients were enrolled (18 men [72.0%] and 7 women [28.0%]; median [IQR] age, 49.0 [43.5-52.5] years). With a median (IQR) follow-up duration of 14.6 months (13.1-16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month progression-free survival was 91.8% (95% CI 91.7% - 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine phosphokinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively. Conclusions: Toripalimab combined with IMRT was tolerable and showed promising antitumor activity in rNPC patients. Clinical trial information: NCT03854838.

Adjuvant high-dose intensity-modulated radiotherapy following radical prostatectomy: Updated 5-year results.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 69-69
Author(s):  
P. Ost ◽  
B. De Potter ◽  
A. Beerens ◽  
N. Lumen ◽  
V. Fonteyne ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Seminal Vesicle ◽  
Gleason Score ◽  
Intensity Modulated Radiotherapy ◽  
High Dose ◽  
Median Dose ◽  
Seminal Vesicle Invasion ◽  
Intensity Modulated ◽  
Gi Toxicity ◽  
Grade 3

69 Background: Approximately 25% of patients treated with immediate post-prostatectomy (adjuvant) radiotherapy will develop a biochemical failure within 5 years after radiotherapy when doses of 60-64 Gy are used. We wanted to report on the safety and biochemical outcome of adjuvant intensity-modulated radiotherapy (AIMRT) with a median dose of 74 Gy. Methods: Between 1999 and 2008, 104 patients underwent a radical prostatectomy followed by AIMRT +/− androgen deprivation (AD). Indications for AIMRT were capsule perforation, seminal vesicle invasion and/or positive surgical margins at prostatectomy specimen. All patients were irradiated at a single tertiary academic centre. AD was initiated in 65% of the patients on the basis of seminal vesicles invasion, pre-prostatectomy PSA > 20ng/mL, Gleason score ≥ 4+3 or personal preference of the referring urologist. A median dose of 74 Gy was prescribed to the planning target volume using IMRT in all patients. AD consisted out of a LHRH analogue for 6 months. The Kaplan-Meier method was used to estimate biochemical relapse-free survival (bRFS). Univariate and multivariate analysis were used to examine the influence of patient- and treatment-related factors on bRFS. Results: The median follow-up was 5 years. Late toxicity: no patients developed grade 3 gastrointestinal (GI) toxicity. Grade 2 GI toxicity was seen in 8%. Seven patients (7%) and 24 (23%) developed grade 3 and 2 genitourinary (GU) toxicity, respectively. An urethral stricture was observed in 8 patients (8%). The 3- and 5-year actuarial bRFS was 91% and 85%, respectively. On univariate analysis bRFS rates was reduced with seminal vesicle invasion (p < 0.04) or Gleason score ≥ 4+3 (p < 0.02) or negative margins (p < 0.001). AD and preoperative PSA levels did not influence bRFS. None of the variables remained significant on multivariate analysis.Eight patients had a distant clinical relapse (pelvic lymph nodes: 3, bone metastases: 3 and 2 patients had both). Seven patients died (3 prostate cancer related deaths). Conclusions: Adjuvant high-dose IMRT after prostatectomy is safe. Five-year bRFS is excellent. No significant financial relationships to disclose.

PET/CT scanning guided intensity-modulated radiotherapy in treatment of recurrent ovarian cancer

2012 ◽  
Vol 81 (11) ◽  
pp. 3551-3556 ◽  
Author(s):  
Xue-lian Du ◽  
Tao Jiang ◽  
Xiu-gui Sheng ◽  
Qing-shui Li ◽  
Cong Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Ct Scanning ◽  
Recurrent Ovarian Cancer ◽  
Intensity Modulated ◽  
Pet Ct

Weekly topotecan for platinum resistant ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15040-15040
Author(s):  
F. Abushahin ◽  
E. C. Grendys ◽  
J. R. Lurain ◽  
D. K. Singh ◽  
A. W. Rademaker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Ca 125 ◽  
Hematological Toxicity ◽  
Secondary Resistance ◽  
Free Survival ◽  
Platinum Resistant ◽  
Significant Difference ◽  
Grade 3

15040 Background: Topotecan is currently used to treat recurrent ovarian cancer after failure of platinum-based therapy. The FDA-recommended regimen (1.5 mg/m2 for 5 consecutive days of a 21-day cycle) is associated with a high incidence of grade 3/4 myelosuppression. Alternate dosing and scheduling may increase patient convenience and reduce toxicity. The objective of this study is to evaluate toxicity, response and progression free survival of weekly topotecan therapy in women with primary and secondary platinum resistant ovarian cancer after failure of 1 or more regimens. Methods: A retrospective analysis of 59 patients that received weekly topotecan with a median dose of 3.75 on days 1, 8, and 15 of a 28-day cycle treated between November 2002 and May 2005. All patients had recurrent epithelial ovarian cancer with primary or secondary resistance to platinum. Disease response was evaluated by CA-125 levels, physical exam, and when appropriate by imaging studies. Toxicity was evaluated using the NCI Common Toxicity Criteria. Results: Response to therapy was noted in (22%) 13 of 59 patients (complete 6.75%, partial 15.25%). Stable disease was noted in 19 patients (32.2%) and progression in 25 patients (42.4%). Two patients (3.4%) had significant side effects that warranted the discontinuation of therapy. There was no significant difference in response to therapy between patients with primary and secondary platinum resistance. A total of 204 cycles were given with a median of 3 (1–12) cycles per patient. Grade 3 and 4 myelosuppression were rare with 1 cycle (0.5%) with grade 3 leukopenia, 15 cycles (6.4%) with grade 3 or 4 neutropenia, 1 cycle (0.5%) with grade 3 anemia, and 1 cycle (0.5%) with grade 3 thrombocytopenia. No patients were admitted with neutropenic fever. The Median Progression-free-survival for responders was 195 days (56–471). Conclusions: Weekly topotecan is a well tolerated and effective regimen for platinum resistant ovarian cancer with considerable less hematological toxicity when compared with historical data for the 5-day regimen. [Table: see text]

A regimen of weekly nab-paclitaxel with weekly carboplatin in recurrent ovarian cancer: A retrospective analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15516-e15516
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
S. P. Somashekhar ◽  
Shabber Zaveri
Keyword(s):  
Ovarian Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
Hypersensitivity Reactions ◽  
Free Survival ◽  
Platinum Resistant ◽  
Number Of Patients ◽  
Grade 3

e15516 Background: The standard of care for patients with recurrent platinum resistant ovarian cancer is treatment with non cross-resistant drugs. Carboplatin retreatment is usually not an option in the platinum resistant population. Weekly paclitaxel has been tried in recurrent patients. But paclitaxel can cause hypersensitivity reactions due to its Cremophor based solvent. nab-paclitaxel being a nano-particle albumin bound paclitaxel is devoid of this toxictity. Also, it is thought that nab-paclitaxel may have a higher intratumoral uptake leading to enhanced anti-tumor action. We looked at a regimen using weekly carboplatin with weekly nab-paclitaxel in platinum resistantrelapsed carcinoma ovary who had failed multiple lines of treatment. Methods: We treated 10 patients with recurrent platinum resistant ovarian cancer with measurable disease with nab-paclitaxel 100mg/m2 on days 1,8,15 with carboplatin at AUC 1.5 on days 1,8,15 intravenously, repeated every 28 days for 4 cycles. All patients had received 3 or more lines of chemotherapy for recurrent disease. We looked for response rate, progression free survival and toxicities. Results: Three patients had complete response, 5 patients had partial response and 2 patients had disease progression. Median PFS was 6 months. There were no instances of paclitaxel induced hypersensitivity reactions. Two patients developed grade 3 neutropenia. One patient developed grade 3 thrombocytopenia. Three patients required blood transfusions. One patient developed grade 3 neuropathy. Conclusions: Weekly combination of nab-paclitaxel with weekly carboplatin is a safe and potentially active treatment in recurrent platinum resistant ovarian cancers who had failed multiple lines of treatment. Considering the efficacy and favorable toxicity profile, this weekly combination needs to be tested in a larger number of patients.

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