Prospective pilot study of consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiotherapy for advanced head and neck cancer

PURPOSE: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. METHODS AND MATERIALS: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m(2), on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gy to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m(2), and cisplatin, 75 mg/m(2), every 3 weeks. RESULTS: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. CONCLUSION: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.     

RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy

To examine combination cisplatin and twice-daily accelerated irradiation (RT) after aggressive transurethral resection of bladder tumor (TURBT) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate, cisplatin, vinblastine (MCV) chemotherapy.Between 1998 and 2000, 52 patients with Stage T2-T4aN0M0 disease, from 17 institutions, were entered into the trial. Forty-seven patients were deemed eligible; the planned accrual was 40. Of the 46 patients, 68% were >60 years old, 70% were men, and 96% had a Karnofsky score >/=90. The clinical T stage was T2 in 66%, T3a in 25%, and T3b in 9%. The median follow-up at the time of analysis was 26 months. The protocol required TURBT within 6 weeks of the initiation of induction therapy. Induction treatment involved 13 days of concomitant boost RT, 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4-6 h later. For sensitization, cisplatin (20 mg/m(2)) was given on the first 3 days of each treatment week. Three to four weeks after induction, patients were evaluated cystoscopically for residual disease. Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation. Patients with residual tumor went on to cystectomy. After either consolidation or cystectomy, patients were to complete three cycles of MCV chemotherapy.Of the 47 patients, 45% completed all phases of the protocol treatment with minor, or no, deviations. Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy. The CR rate after induction therapy was 74%. For 2 patients, residual disease after induction was limited to positive cytologic findings, and for 8 patients, biopsy of the primary site revealed persistence. Of the 8 cystectomy patients, 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen. Grade 3 toxicity related to chemotherapy was observed in 11% of patients during both induction and consolidation, and in 41% during adjuvant chemotherapy. A total of 8 patients (36% of those receiving adjuvant chemotherapy) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy. Grade 3 toxicity due to RT was seen in 4% and 0% of patients during induction and consolidation, respectively. One patient developed Grade 4 hydronephrosis during consolidation. The projected 36-month value for locoregional failure, distant metastasis, overall survival, and bladder-intact survival was 27%, 29%, 61%, and 48%, respectively.After aggressive TURBT, twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response (74%) similar to that in previous bladder-sparing trials. The projected 2-year values for locoregional control, bladder-intact survival, and overall survival were also consistent with previously reported trials of bladder-sparing treatment. With only 45% of patients completing three cycles of MCV, this form of adjuvant chemotherapy appears to be poorly tolerated by most patients.     

Phase II study of consolidation chemotherapy after concurrent chemoradiation in cervical cancer: preliminary results

PURPOSE: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. METHODS AND MATERIALS: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m(2) (Day 1) and 5-fluorouracil 1000 mg/m(2) (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. RESULTS: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). CONCLUSIONS: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.     

局部进展期直肠癌术前3DCRT与VMAT同期化疗远期疗效比较

目的:比较术前三维适形放疗(3DCRT)与容积调强弧形治疗(VMAT)同期化疗用于局部进展期直肠癌(LARC)的5年总生存(OS)及无进展生存(DFS)结果,并分析该新辅助模式下的诱导/巩固化疗的价值。方法:回顾收集2007—2013年间在中山大学肿瘤防治中心接受术前3DCRT或VMAT同期联合化疗(主要为Xelox方...     

Neoadjuvant versus Adjuvant Chemotherapy in Patients with Resectable Muscle-Invasive Bladder Cancer

Introduction: In regards to resectable muscle-invasive bladder cancer (MIBC) patients, contemporary guidelines recommend treatment with radical cystectomy and perioperative chemotherapy (neoadjuvant or adjuvant). In addition, the 5-year survival rate ranges from 36% to 48% in connection to T3 or T4 staged tumors or lymph node metastatic tumors. Perioperative treatment can improve overall survival, and the most robust evidence are in favor of neoadjuvant chemotherapy. The purpose of this study was to assess the impact of perioperative chemotherapy on the survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC). Methods: The medical records of ninety-four patients with muscle-invasive bladder cancer (MIBC) that were treated with radical cystectomy and perioperative chemotherapy from 2008 to 2018 were retrospectively analyzed at Songklanagarind hospital. Neoadjuvant and adjuvant chemotherapy groups were classified. Univariable and multivariable regression analyses were used to predict overall survival (OS) after treatment. The survival rates for each group were estimated and compared using long-rank testing. Results: Overall, we identified 94 eligible patients of whom 20 patients (21.2%) received neoadjuvant and 74 patients (78.8%) received adjuvant chemotherapy. The 5-year survival rate of the neoadjuvant group was 55.7%, and in regards to the adjuvant group it was 30.4%. A multivariable analysis yielded that, patients treated with neoadjuvant chemotherapy had longer survival than those treated with adjuvant chemotherapy (p =0.039).  The median survival here as log rank compares median survival. Conclusion: The overall survival of neoadjuvant chemotherapy (NAC) was better than adjuvant chemotherapy (AC) in regards to muscle-invasive bladder cancer. These data could support the use of neoadjuvant chemotherapy in MIBC prior to radical cystectomy.     

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas

AIM: To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma (NPC).METHODS: We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy (CCRT) (22/40 patients) or CCRT alone (18/40) from March 2006 to March 2012. Patients underwent fiberoscopy with biopsy of the primitive tumor, and computed tomography scan of head, neck, chest and abdomen with and without contrast. Cisplatin was used both as induction and as concomitant chemotherapy, while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions (total dose, 70 Gy). The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly. This retrospective analysis was approved by the review boards of the participating institutions. Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS: Thirty-three patients were males and 7 were females. Median follow-up time was 58 mo (range, 1-92 mo). In the sub-group of twenty patients with a follow-up time longer than 36 mo, the 3-year survival and disease free survival rates were 85% and 75%, respectively. Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%. Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients. Grade 2 mucositis was seen in 29 patients, while grade 2 xerostomia was seen in 30 patients. Overall toxicity was manageable and it did not cause any significant treatment delay. In the whole sample population, long term toxicity included grade 2 xerostomia in 22 patients, grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION: Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC. The role of adjuvant chemotherapy remains to be defined.     

Carboplatin plus paclitaxel and sequential radiation followed by consolidation carboplatin and paclitaxel in patients with previously untreated locally advanced NSCLC. A Hoosier Oncology Group (HOG) phase II study

Chemoradiation is standard treatment for patients with unresectable locally advanced non-small cell lung cancer (NSCLC). However, local and distant relapse rates remain high. It has been postulated that the addition of consolidation chemotherapy might further decrease the systemic relapse rate. We performed this phase II study to evaluate the toxicities and activity of two cycles of paclitaxel and carboplatin administered prior to and following thoracic radiation in patients with locally advanced, inoperable NSCLC. From April to December 1997, 25 patients were entered on study. Twenty-three patients were eligible and received paclitaxel 225 mg/m(2) intravenously over 3 h followed by carboplatin at an AUC (6) on days 1 and 22. Radiation consisted of 60 Gy given over 6 weeks beginning on day 43. Patients with non-progressive disease received two additional cycles of consolidation carboplatin and paclitaxel. Four of 23 patients progressed during induction chemotherapy. There were seven PR's and 11 had SD after induction chemotherapy. Following radiation, the response changed to 11 PR, four SD, and three had progressive disease. Of the 15 patients eligible to receive consolidation chemotherapy, three were excluded due to a poor performance status. Twelve patients were treated with consolidation chemotherapy with further improvement in two patients (SD to PR, PR to CR). All 12 patients who received consolidation chemotherapy developed grade 3 or 4 neutropenia, including three patients with neutropenic fever. The overall response rate was 52.1%. The median survival, 1-, and 2-year survival was 10.5 months, 45, and 17%, respectively. In conclusion, consolidation chemotherapy was associated with significant hematologic toxicity without an obvious improvement in survival in comparison to other studies utilizing chemoradiation alone.     

Phase II study of irinotecan plus cisplatin induction followed by concurrent twice-daily thoracic irradiation with etoposide plus cisplatin chemotherapy for limited-disease small-cell lung cancer.

PURPOSE: Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-na?ve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC). PATIENTS AND METHODS: Between November 2001 and May 2003, 35 chemotherapy-na?ve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m2 and irinotecan 80 mg/m2 intravenously (i.v.) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m2 i.v. on days 43 and 64, and etoposide 100 mg/m2 i.v. on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43. RESULTS: All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT. CONCLUSION: IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.     

新辅助与辅助膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌的疗效对比

 目的 探讨经尿道膀胱肿瘤电切术（TURBT）术前新辅助膀胱热灌注化疗对比术后辅助膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌的疗效。方法 收集经尿道膀胱肿瘤电切术术前或术后使用BR-TRG-Ⅱ型体腔热灌注治疗仪行吉西他滨膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌患者40例,其中16例行术前（吉西他滨1000 mg,45℃,45 min）新辅助膀胱热灌注化疗3次,隔天一次,治疗结束后3~7天行经尿道膀胱肿瘤电切术,定义为新辅助组;另外24例患者先行TURBT手术,术后即刻或者隔天（吉西他滨1000 mg,45℃,45 min）行辅助膀胱热灌注化疗,定义为辅助组。记录并比较两组患者无疾病复发生存期（RFS）以及不良反应。结果 全部40例患者均完成3次吉西他滨膀胱热灌注化疗,新辅助组患者中,完全缓解（pT0）11例（68.8%）,部分缓解5例（31.2%）。新辅助组中位无复发生存期为54月,辅助组中位无复发生存期为45月,两者比较差异无统计学意义（P=0.3146）。两组患者不良反应可耐受。结论 无论是新辅助还是辅助治疗,使用BR-TRG-Ⅱ型体腔热灌注治疗仪行吉西他滨膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌安全有效。     

Randomized Phase II Trial Comparing Chemoradiotherapy with Chemotherapy for Completely Resected Unsuspected N2-Positive Non–Small Cell Lung Cancer

IntroductionWe investigated whether concurrent chemoradiotherapy (CCRT) would increase survival in patients with completely resected unsuspected N2-positive NSCLC versus in patients who received adjuvant chemotherapy alone.MethodsEligible patients were randomly assigned (1:1) to either the CCRT arm or the chemotherapy arm. In the CCRT arm, patients received concurrent thoracic radiotherapy (50 Gy in 25 fractions) with five cycles of weekly paclitaxel (50 mg/m²) and cisplatin (25 mg/m²), followed by two additional cycles of paclitaxel (175 mg/m²) plus cisplatin (80 mg/m²) at 3-week intervals. In the chemotherapy arm, patients received four cycles of adjuvant paclitaxel (175 mg/m²) and carboplatin (area under the curve = 5.5) every 3 weeks. The primary end point was disease-free survival.ResultsWe enrolled and analyzed 101 patients (51 received CCRT and 50 received chemotherapy). In all, 74 and 27 patients were preoperatively staged as N0 and N1 diseases, respectively. The baseline characteristics were well balanced between the two arms. The median disease-free survival of the CCRT arm was 24.7 months, which was not significantly different from that of the chemotherapy arm (21.9 months) (hazard ratio = 0.94, 95% confident interval: 0.58–1.52, p = 0.40). There was no difference in overall survival (74.3 months in CCRT arm and 83.5 months in the chemotherapy arm) (hazard ratio = 1.33, 95% confident interval: 0.71–2.49).ConclusionsThere was no survival benefit from adjuvant CCRT compared with from platinum-based chemotherapy alone for completely resected unsuspected N2-positive NSCLC. However, the role of sequential radiotherapy administered after adjuvant chemotherapy is being evaluated, and further study is needed to evaluate the optimal radiotherapy approach for completely resected N2-positive NSCLC.     

Concurrent Cisplatin,Prolonged Oral Etoposide,and Vincristine plus Chest and Brain Irradiation for Limited Small Cell Lung Cancer: A Phase II Study of the Southwest Oncology Group (SWOG-9229)

Purpose: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting.Methods and Materials: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m² i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m² (days 1–14, 29–42, and 57–70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m² i.v., doxorubicin 50 mg/m² i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy.Results: Among 56 eligible patients, 93% had SWOG performance status 0–1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimun follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary fibrosis (including one Grade 3) and six cases of pneumonitis (including one Grade 3).Conclusion: Concomitant chemoradiation with oral etoposide as part of a platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is not better than our prior best group-wide experience. The progression-free and overall survival are similar to published trials utilizing short-course i.v. etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent advantage to prolonged exposure to etoposide, and toxicity resulted in an inferior therapeutic index compared to programs with shortened exposure.     

Therapy studies of the German Hodgkin's Study Group. Intermediate results of the study protocols HD1, HD2, and HD3

Between July 1983 and September 1986 358 untreated patients with Hodgkin's lymphoma qualified for the protocols HD1 (stages I to IIIA with risk factors), HD2 (stage IIIA), and HD3 (stages IIIB and IVAB). Patients in HD1 received a combined chemo-radiotherapy (2 X COPP/ABVD + 40 Gy EF vs. 2 X COPP/ABVD + 20 Gy EF). Patients in HD2 were randomized into radiotherapy (TNI 40 Gy) vs. combined chemo-radiotherapy (2 X COPP/ABVD + 20 Gy IF). Patients in HD3 received induction chemotherapy (3 X COPP/ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 X COPP/ABVD). In HD1, 51 out of 65 evaluable patients (78%) achieved a complete remission. The survival of HD1 patients is as good as the survival of patients in stages I and II without risk factors. In HD3, 58 out of 93 patients (62%) achieved complete remission after induction chemotherapy with COPP/ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 71% complete remissions in stages IIIB/IVAB were achieved. The progression-free survival of HD3 patients who received consolidation therapy is significantly longer than of patients who refused consolidation therapy.     

Induction Chemotherapy (Cisplatin + 5-Fluorouracil) and Radiotherapy in Advanced Squamous Cell Carcinoma of the Head and Neck

A phase 11 study was made of 58 consecutive patients with previously untreated locally advanced squamous cell carcinomas of the head and neck. The induction chemotherapy consisted of 3 courses of cisplatin (100mg/m²) and a subsequent 120-h infusion of 5-fluorouracil (1 000 mg/m²/24 h) repeated every 3 weeks. It was followed by radiotherapy to a median target dose of 66 Gy and surgery for residual tumour. A total of 91 per cent received all 3 courses of chemotherapy, which was well tolerated. Complete response (CR) was obtained in 20 patients (35%) after chemotherapy and in 40 patients (69%) after subsequent radiotherapy. The median observation time was 28 months (range 15-57). The actuarial survival at 2 years for complete responders to chemotherapy was 83 per cent, implying a prolonged survival (p = 0.002) compared to those with less than CR. Complete responders after chemotherapy had also a significantly longer recurrence-free survival, though 19 out of 20 did not undergo surgery. Complete response after this induction therapy is thus an important prognostic predictor.     

新辅助化疗与辅助化疗治疗肌层浸润性膀胱癌的疗效比较

 目的 对接受新辅助和辅助化疗的膀胱癌患者临床疗效进行对比，为化疗时机的选择作初步探索。方法 回顾性研究湖北省肿瘤医院2009—2016年诊断为肌层浸润性膀胱癌并在全膀胱术前（新辅助）或术后（辅助）接受了GC方案化疗的患者。主要研究终点是无复发生存期（recurrencefree survival, RFS）。次要研究终点是临床完全缓解率（complete response, CR）。结果 共38例肌层浸润性膀胱癌患者纳入研究（22例新辅助+16例辅助）。在中位随访时间点时，新辅助和辅助化疗组的RFS相比较差异无统计学意义（69.6% vs.75.4%, P=0.223）。在中位随访时间点上接受新辅助化疗后病理完全缓解组（pT0）与非完全缓解组（non-pT0）的RFS分别为100%和50%（P=0.012），差异有统计学意义。两组患者在接受化疗治疗后出现3~4级严重血液学不良反应的人数比例相比较差异无统计学意义（P=0.36）。结论 接受新辅助或辅助化疗的肌层浸润性膀胱癌患者的RFS相比较差异无统计学意义，新辅助化疗后达到病理完全缓解的患者均未出现肿瘤复发，但尚需更多的研究来证实。     

Adjuvant concurrent chemoradiotherapy with intensity-modulated pelvic radiotherapy after surgery for high-risk, early stage cervical cancer patients

PURPOSE: This study was undertaken to assess local control and toxicity with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy (CCRT) for early stage cervical cancer. PATIENTS AND METHODS: Between June 2004 and February 2007, 54 patients with early stage cervical cancer (stage IB-IIA) with high-risk factors for treatment failure after surgery were treated with adjuvant pelvic IMRT and CCRT. Adjuvant chemotherapy consisted of cisplatin (50 mg/m2) weekly for 4 to 6 courses. All the patients received 50.4 Gy of external beam radiotherapy with IMRT in 28 fractions and 6 Gy of high-dose rate vaginal cuff brachytherapy in 3 insertions. RESULTS: Adjuvant CCRT with IMRT provided good local tumor control in posthysterectomy cervical cancer patients with high-risk pathologic features. The 3-year locoregional control and disease-free survival were 93% and 78%, respectively. Histology and lymph node metastasis were indicators for disease-free survival. Low acute and chronic treatment-related toxicities were noted with IMRT. All the patients completed the radiotherapy treatment without any major toxicity. In terms of chronic toxicity, only 1 patient had grade 3 genitourinary toxicity and none had grade 3 gastrointestinal toxicity. CONCLUSION: Our results indicate that adjuvant CCRT with IMRT technique for adjuvant treatment of early stage cervical cancer is associated with excellent local control and low toxicity.     

Concurrent cisplatin, 5-fluorouracil,leucovorin, and radiotherapy for invasive bladder cancer

PURPOSE: To investigate the tolerance and efficacy of a modified concurrent chemoradiation (CCRT) protocol for patients with invasive bladder cancer "unfit" for radical cystectomy. METHODS AND MATERIALS: Twenty-three muscle-invasive bladder cancer patients who were unfit for or unwilling to receive radical cystectomy were enrolled in this study. All patients had transitional cell carcinoma of bladder, and distribution of stage was 14 (61%), 1 (4%), and 8 (35%) for T3a, T3b, and T4, respectively. This study included a relatively old-age population, with the median age being 75 and 70% of patients over 70 years old. Patients were treated with maximal transurethral resection of the bladder tumor followed by curative CCRT. The chemotherapy (C/T) regimen was comprised of cisplatin, 50 mg/m(2) intravenously (i.v.) on Day 1; 5-fluorouracil (5-FU), 500 mg/m(2)/day by continuous i.v. infusion on Days 1-3; and leucovorin, 50 mg/day by continuous i.v. infusion on Days 1-3. Chemotherapy course was repeated at 21-day intervals. The radiation dose was 44-45 Gy to whole pelvis and 60-61.2 Gy to bladder, with a daily fraction of 1.8-2 Gy. The completeness of the CCRT protocol was defined as patients receiving at least 55 Gy of radiotherapy to the whole bladder and at least three courses C/T. RESULTS: Seventy-four percent of patients (17/23) completed the CCRT protocol. Radiation Therapy Oncology Group (RTOG) Grade 3 acute toxicities were observed in 4 patients, which included leucopenia, vomiting, genitourinary (GU) tract infection, and diarrhea. No treatment-related deaths occurred during the CCRT period. RTOG Grade 3 or more late complications were observed in 3 patients; one of them died of radiation cystitis superimposed with GU infection. Of the 18 patients whose response to CCRT was evaluated, a complete tumor response was documented in 16 patients (89%). With a median follow-up of 3 years, the 3-year overall survival (OS) and disease-free survival (DFS) for all patients was 69% and 65% respectively. Meanwhile, the 3-year overall and DFS rates for patients who completed CCRT vs. those who did not complete CCRT were 82% vs. 33% and 75% vs. 33%, respectively (p = 0.18 for OS and p = 0.04 for DFS). CONCLUSIONS: Concurrent cisplatin, 5-FU, leucovorin, and radiotherapy for treatment of invasive bladder cancer is a feasible and promising treatment even for relatively old patients. Our results are comparable to those in recent studies by using combined modality treatment or neoadjuvant chemotherapy plus radical cystectomy. Consequently, this novel protocol warrants a prospective clinical trial and may be a safe, effective alternative to radical cystectomy.     

Comparison of Radical Cystectomy and Chemoradiotherapy in Patients with Locally Advanced Bladder Cancer

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followedby radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033)but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.     

Concurrent Cisplatin, Prolonged Oral Etoposide, and Vincristine plus Chest and Brain Irradiation for Limited Small Cell Lung Cancer: A Phase II Study of the Southwest Oncology Group (SWOG-9229)

Purpose: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting.

Methods and Materials: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m² i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m² (days 1–14, 29–42, and 57–70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m² i.v., doxorubicin 50 mg/m² i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy.

Results: Among 56 eligible patients, 93% had SWOG performance status 0–1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimun follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary fibrosis (including one Grade 3) and six cases of pneumonitis (including one Grade 3).

Conclusion: Concomitant chemoradiation with oral etoposide as part of a platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is not better than our prior best group-wide experience. The progression-free and overall survival are similar to published trials utilizing short-course i.v. etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent advantage to prolonged exposure to etoposide, and toxicity resulted in an inferior therapeutic index compared to programs with shortened exposure.     

Induction Docetaxel and Cisplatin Followed by Weekly Docetaxel and Cisplatin with Concurrent Radiotherapy in Locally Advanced Stage III Non Small Cell Lung Cancer (LA-NSCLC)-A Phase II Study

Purpose: The objective of this phase II study was to document the activity and to evaluate the toxicity of docetaxel and cisplatin as induction chemotherapy followed by concurrent docetaxel and cisplatin with thoracic radiation in locally advanced stage III non small cell lung cancer. Patients and Methods: Twenty-seven patients with stage III locally advanced non-small cell lung cancer received induction chemotherapy with two cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 D1 every 3 weeks. Patients without disease progress after induction chemotherapy were assigned to concurrent chemoradiotherapy 20mg/m2 docetaxel&25mg/m2 cisplatin administrated on day 1 every week for 6 weeks along with concurrent radiotherapy at a dose of 60Gy in 30 fractions (2 Gy/fraction and 5 fractions per week). The primary endpoint was to determine the overall response rate (ORR), the secondary endpoint was to evaluate time to progression (TTP) and safety profile. Results: After induction chemotherapy, the overall response rate (ORR) was 44.4%, 23 patients without disease progress were assigned to concurrent treatment with an overall response rate of 65%. Median survival time was 17 months, time to progression was 11.5 months and the one-year survival was 58%. Neutropenia was the most common toxicity during induction therapy (26% expressed grade 3-4) whereas esophagitis was the most common toxicity during concurrent phase (17.3% expressed grade 3-4); toxicities were manageable. Conclusion: Induction chemotherapy by docetaxel and cisplatin followed by weekly docetaxel and cisplatin with concurrent thoracic radiation therapy is feasible and tolerable. These results warrant further large randomized studies to document and confirm the effectiveness of this regimen. Key Words: Lung cancer , Docetaxel , Cisplatin , Concurrent chemoradiotherapy.     

Study Protocol of the Bladder Adjuvant RadioTherapy (BART) Trial: A Randomised Phase III Trial of Adjuvant Radiotherapy Following Cystectomy in Bladder Cancer

AimsTo assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy.Materials and methodsThe BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy – Colorectal questionnaire is recorded pre-treatment and at follow-up.Endpoints and statisticsThe primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life.ConclusionThe BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC.