The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

Objective

To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer.

Methods

We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m² cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m²/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin.

Results

Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease.

Conclusion

CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated.     

Concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil (5-FU) and cisplatin for locally advanced resectable esophageal cancer

Background

Neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment for esophageal cancer (EC) in North America. The cisplatin/5-flurouracil (5-FU) combination has been the most commonly used regimen. For the last 15 years we incorporated a daily continuous infusion of 5-FU and 2 doses of cisplatin into our neoadjuvant CCRT for potentially resectable EC.

Patients and methods

Between July 1997 and June 2012, 129 patients with locally advanced EC (T3 or N1 and higher), received neoadjuvant CCRT with cisplatin 75 mg/m² on day 1 and day 29 and continuous infusion of 5-FU (225 mg/m²/day) on the days of radiation.

Results

The median age of patients was 63 years, 85% had adenocarcinoma, 29, 74 and 26 patients had stage II, III and IVa disease respectively, 110 patients had N1 disease based on the American Joint Committee on Cancer (AJCC) 6^th edition, 118 patients experienced weight loss during treatment. All patients completed treatment. Treatment was well tolerated with 14% of patients having ≥ grade 3 toxicity and 18 patients requiring hospital admission. Sixty-four percent of patients had surgical resection following CCRT, with disease progression and patient refusal being the most common reasons for not proceeding with surgery. An R0 resection was achieved in 96% of patients. A pathological complete response (pCR) was achieved in 45% of patients. With a median follow up of 26 months (1.2-144 months), 48/129 patients recurred and 60/129 died of their disease.

Conclusions

Our study has its limitation, however, and compared to the conventional chemotherapy regimens containing the cisplatin/5-FU doublet, our treatment strategy for locally advanced EC CCRT seems to be feasible and well tolerated.     

Comparison of Carboplatin‐ and Cisplatin‐Based Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer Patients With Morbidity Risks

Purpose.

The aim of this study was to assess the activity and toxicity of primary carboplatin-based chemoradiotherapy (CarboRT) and to compare CarboRT with cisplatin-based chemoradiotherapy (CisRT) in patients with locally advanced cervical cancer and poor general condition.

Patients and Methods.

Fifty-one locally advanced cervical cancer patients with morbidity risks were prospectively enrolled between January 2007 and April 2010. Eligible patients received weekly intravenous CarboRT with carboplatin 100 mg/m², and a comparison was made with a historical patient group that received weekly CisRT with cisplatin 40 mg/m².

Results.

Median follow-up was 36 months (range: 4–66 months) in the CarboRT group and 53 months (range: 4–121 months) in the CisRT group. Compared with the historical CisRT group, the CarboRT group showed no statistically significant differences in recurrence (hazard ratio [HR], 1.21; 95% confidence interval [CI], 0.52–2.81) and survival (HR, 1.80; 95% CI, 0.49–6.54). The mean numbers of received cycles of CarboRT and CisRT were 7.5 ± 1.4 and 6.0 ± 1.8, respectively (p < .001). The rates of grade 3–4 toxicity were similar in the two groups.

Conclusions.

CarboRT was better tolerated than CisRT without compromising tumor response and survival in patients with locally advanced cervical cancer and poor general condition.     

Comparison of concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil versus cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma

Objective

The aim of this study was to compare survival outcomes and toxicities between concurrent radiotherapy with cisplatin plus 5-fluorouracil and that with cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma.

Methods

We retrospectively reviewed data from 93 locally advanced cervical carcinoma patients (stage IB to IVA) who had been treated by concurrent radiotherapy with cisplatin plus 5-fluorouracil (CF, n=45) vs. cisplatin plus paclitaxel (CP, n=48) as primary therapy. Toxicities and survival outcomes were compared.

Results

In the CP group, there were higher frequencies of severe (grade 3 or 4) leukopenia (79.2%, as compared to 11.1% in the CF group), severe neutropenia (77.1%, as compared to 8.9% in the CF group) and severe peripheral neuropathy (12.5%, as compared to 2.2% in the CF group). In the CF group, there were higher frequencies of severe nausea (33.3%, as compared to 14.6% in the CP group) and severe hyponatremia (11.1%, as compared to 0% in the CP group). Five-year DFS of the CF and CP groups was 67.4% and 79.1%, respectively (p=NS). Five year OS of the CF and CP groups was 79.6% and 80.9%, respectively (p=NS).

Conclusion

Concurrent radiotherapy with cisplatin plus paclitaxel showed increased leukopenia, neutropenia and peripheral neuropathy, but less gastrointestinal toxicity (nausea) than that with cisplatin plus 5-fluorouracil. Survival outcome between these two groups was not statistically different in this study. Large prospective randomized controlled studies will be needed to confirm this result.     

Efficacy and tolerability of paclitaxel,ifosfamide, and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical carcinoma

Objective

To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma.

Methods

Patients with histologically confirmed locally advanced cervical carcinoma, aged ≥18 years, were treated with intravenous ifosfamide 5,000 mg/m² and mesna 5,000 mg/m², on day 1; intravenous paclitaxel 175 mg/m² and cisplatin 75 mg/m², on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy.

Results

One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively.

Conclusion

Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.     

Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort

Objective

Concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer. We studied prognostic factors for patients treated with CCRT.

Methods

We retrospectively reviewed records of 85 consecutive patients with cervical cancer who were treated with CCRT between 2002 and 2011, with external beam radiation therapy, intracavitary brachytherapy, and platinum-based chemotherapy. Survival data were analyzed with Kaplan-Meier methods and Cox proportional hazard models.

Results

Of the 85 patients, 69 patients (81%) had International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease; 25 patients (29%) had pelvic lymph node enlargement (based on magnetic resonance imaging), and 64 patients (75%) achieved clinical remission following treatment. Median maximum tumor diameter was 5.5 cm. The 3- and 5-year overall survival rates were 60.3% and 55.5%, respectively. Cox regression analysis showed tumor diameter >6 cm (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2 to 4.6), pelvic lymph node enlargement (HR, 2.2; 95% CI, 1.1 to 4.5), and distant metastasis (HR, 10.0; 95% CI, 3.7 to 27.0) were significantly and independently related to poor outcomes.

Conclusion

New treatment strategies should be considered for locally advanced cervical cancers with tumors >6 cm and radiologically enlarged pelvic lymph nodes.     

Outcomes of advanced and recurrent cervical cancer treated with cisplatin and generic topotecan: retrospective analysis in a tertiary care hospital in Thailand

Objective

Retrospective evaluation of the outcome of stage IVB, recurrent or persistent cervical cancer treated with cisplatin and generic topotecan (CT) in a tertiary care hospital in Thailand.

Methods

The medical records of patients treated with CT regimen at Chiang Mai University Hospital between January 2005 and December 2007 were reviewed and analyzed. The treatment protocol consisted of IV topotecan 0.75 mg/m² on days 1, 2, and 3; combined with cisplatin 50 mg/m² IV on day 1 and repeated every 21 days until progression or unacceptable toxicity for a maximum of 6 cycles. The outcomes were evaluated based on the response rate, progression free survival (PFS), and overall survival (OS) by using the World Health Organization criteria. The adverse effects of the treatments were also determined.

Results

Twenty-one cervical cancer patients received the CT regimen. The tumor response rate was 28.6%. The median PFS and OS was 4 and 11 months, respectively. With 87 cycles of chemotherapy, the most common grade 3 & 4 hematologic toxicity was neutropenia (57.9%).

Conclusion

Advanced and recurrent cervical cancer patients treated with cisplatin and generic topotecan had a favorable outcome with manageable toxicity.     

Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer

Objective

To assess the toxicity of delivering extended field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for locally advanced cervical carcinoma.

Methods

Forty-five patients who underwent EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to IIIB cervical cancer were retrospectively reviewed. The clinical target volume included all areas of gross and potentially microscopic disease and regional lymph node regions. All patients underwent high-dose-rate brachytherapy. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively.

Results

The median follow-up was 28 months (range, 5 to 62 months). Forty-two patients had a complete response, and three had a persistent disease. Of those 42 patients, 15 patients (35.7%) had recurrence. The regions of recurrence were in-field in 2 patients and out-field in 13 patients. Acute grade ≥3 gastrointestinal, genitourinary and hematologic toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%) suffered from late grade 3 toxicities. Seven patients experienced ovarian transposition, 5 of those patients (71%) maintained ovarian function. Thirty-eight patients (84.4%) were alive at the last follow-up.

Conclusion

Concurrent cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are acceptable. EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.     

Survival benefit of laparoscopic surgical staging-guided radiation therapy in locally advanced cervical cancer

Objective

This study was designed to evaluate the survival benefit of laparoscopic surgical staging (LSS)-guided tailored radiation therapy (RT) in locally advanced cervical cancer (LACC).

Methods

We retrospectively reviewed 89 LACC patients'' medical records who primarily received non-surgical treatment, of which pretreatment LSS was performed in 20 (LSS group) and primary chemoradiation therapy (CCRT) without LSS (CCRT group) was carried out in 69 from January 2000 to January 2006. We analyzed clinical characteristics, pretreatment imaging study results and survival outcomes including disease free survival (DFS) and overall survival (OS) to compare them between the two groups.

Results

There were as many as eight cases (40%) of LSS related complications. The mean time interval between LSS and RT or CCRT was 26.6 days (±18.8 days). Six out of twenty (30%) in LSS group and 10 out of 69 (14.5%) in CCRT group received extended field RT when paraaortic lymph nodes (LNs) were positive based on the pathologic findings after LSS and the results of imaging studies, respectively. Three-year DFS and OS were both better in 33 imaging-negative CCRT group patients than those in 4 imaging-negative/pathology-positive (false negative) patients after LSS (3-year DFS, 50% vs. 87%, p=0.022; 3-year OS, 50% vs. 84%, p=0.033). The 5-year DFS rates were 52% and 55% in LSS group and in CCRT group, respectively (p=0.28). The 5-year OS rates were 68% in LSS group and 62% in CCRT group without significant difference between the two groups (p=0.79).

Conclusion

We found that LSS-based RT tailoring did not show survival benefit in LACC despite inaccuracy of imaging-based RT tailoring. Further studies are required to find new method to overcome this inaccuracy and improve survival outcomes.     

Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally advanced squamous cell carcinoma of the vulva

Objective

The therapeutic outcomes of patients with advanced vulvar cancer are poor. Multi-modality treatments including concurrent chemoradiation or different regimens of neoadjuvant chemotherapy (NACT), and surgery have been explored to reduce the extent of surgery and morbidity. The present single-institution trial aimed to evaluate the efficacy and toxicity of paclitaxel and cisplatin in locally advanced vulvar cancer.

Methods

From 2002 to 2009, 10 patients with stage III-IV locally advanced squamous cell carcinoma of the vulva were prospectively treated with 3 courses of paclitaxel-ifosfamide-cisplatin or paclitaxel-cisplatin. Nine of them subsequently underwent radical local excision or radical partial vulvectomy and bilateral inguino-femoral lymphadenectomy.

Results

The clinical response rate of all enrolled patients was 80%, whereas the pathological responses included 1 case with complete remission, 2 with persistent carcinoma in situ, and 6 invasive cancer cases with tumor shrinkage of more than 50%. Four patients had positive nodes. Forty percent of patients experienced grade 3-4 bone marrow toxicity, which was successfully managed with granulocyte-colony stimulating factor, even in cases of elderly patients. Median progression-free survival after surgery was 14 months (range, 5 to 44 months). Six of the 7 recurrent cases were local, and 3 of them were treated with salvage surgery while the other 3 received radiation with or without chemotherapy. After a median follow-up period of 40 months (range, 5 to 112 months), 55.5% of patients remained alive with no evidence of disease, including 2 long-term survivors after recurrence at 5 and 9 years.

Conclusion

Based on the high response rate and manageable toxicity, NACT with paclitaxel and cisplatin with or without ifosfamide followed by surgery could be considered as a therapeutic option for locally advanced vulvar cancer.     

A Randomized,Multicenter, Phase II Study of Cetuximab With Docetaxel and Cisplatin as Induction Chemotherapy in Unresectable,Locally Advanced Head and Neck Cancer

Lessons Learned

• Addition of cetuximab may affect tolerability and, in turn, affect eventual outcomes.
• The incidence of prior human papillomavirus infection has emerged as an important variable that can confound trials enrolling patients with oropharyngeal cancer.

Background.

We investigated the efficacy of cetuximab when added to induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck squamous cell carcinoma.

Methods.

Patients were randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy. Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas patients in the TP arm received cisplatin alone. The primary endpoint was the objective response rate (ORR) after induction chemotherapy.

Results.

Overall, 92 patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP arms were not different (81% vs. 82%). Adding cetuximab lowered the completion rate of induction chemotherapy and CCRT and resulted in more frequent dose reductions of the induction chemotherapy, although this did not reach statistical significance. In the CTP and TP arms, respectively, the 3-year progression-free survival (PFS) rates were 70% and 56% (p = .359), and the overall survival (OS) rates were 88% and 74% (p = .313). When limited to patients who completed induction chemotherapy, 3-year PFS rates of 78% and 59% (p = .085) and OS rates of 94% and 73% (p = .045) were observed in the CTP and TP arms, respectively.

Conclusion.

Adding cetuximab to sequential treatment did not increase the treatment efficacy and resulted in greater toxicity. In the intent-to-treat population, neither PFS nor OS was improved by the addition of cetuximab to sequential treatment; however, a suggestion of improved survival outcomes was observed in patients completing cetuximab-containing induction chemotherapy.     

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients

Background

The objective of this study was to evaluate the efficacy and safety of pemetrexed plus cisplatin/carboplatin in locally advanced or metastatic non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy.

Methods

Fifty-three locally advanced or metastatic non-small cell lung cancer patients previously treated with platinum-based chemotherapy received pemetrexed 500 mg/m² plus cisplatin 75 mg/m² or carboplatin area under the curve (AUC) 5 every 21 days, with dexamethasone, folic acid and vitamin B12 being administered.

Results

Median age was 52 years. Eastern Cooperative Oncology Group (ECOG) performance status was 0-2. Thirty-eight patients had stage IV tumors. Thirty-seven patients had adenocarcinoma (including 6 alveolar carcinoma patients), and fourteen patients had squamous cell carcinoma. Thirty-four patients were treated in second line, 15 in third line, and 4 in fourth line. Seven patients (13.2%) showed partial response; Thirty-six (67.9%) had stable disease. The median progression free survival time was 6.0 months and the median overall survival time was 10.0 months. The 1-year survival rate was 40.9%. Five (9.4%) and four (7.5%) patients experienced grade 3 or 4 leukopenia and thrombocytopenia, respectively. Nonhematological toxicities included grade 3 nausea/vomiting in 1 patient (1.9%), grade 3 rash in 1 patient, grade 4 diarrhea in 1 patient (1.9%) and grade 4 creatinine increase in 1 patient (1.9%).

Conclusion

Locally advanced or metastatic NSCLC patients previously treated with platinum-based chemotherapy could benefit from pemetrexed plus cisplatin/carboplatin chemotherapy with tolerable adverse events.     

Phase II trial of docetaxel,cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001)

Background:

Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease.

Methods:

Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m⁻² day 1, cisplatin 60 mg m⁻² day 1, 5-flurouracil 750 mg m⁻² per day days 1–5, repeated every 3 weeks). Primary outcome was objective response (assessed by RECIST). Fourteen or more responses in 26 evaluable patients were required to confirm a response rate of 60% or higher (Fleming-A''Hern design), warranting further evaluation. Secondary endpoints included toxicity and survival.

Results:

10/26 evaluable patients (38.5%, 95% CI: 20.2–59.4) achieved an objective response. Two patients with locally advanced disease achieved radiological complete remission. 65.5% of patients experienced at least one grade 3/4 adverse event.

Conclusion:

Docetaxel, cisplatin and 5FU did not reach the pre-determined threshold for further research and caused significant toxicity. Our results do not support the routine use of TPF. The observed complete responses support further investigation of combination chemotherapy in the neoadjuvant setting.     

Concurrent chemoradiation followed by adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma in Korea

Purpose

Concomitant approach using cisplatin and 5-fluorouracil (5-FU) has shown an excellent local control rate and significantly reduced distant metastasis in patients with locally advanced nasopharyngeal carcinoma (NPC). However, optimal schedule and dosing of chemotherapy still need to be developed to reduce distant metastasis. This retrospective study was conducted to evaluate the efficacy, toxicity, and tolerability of a concurrent chemoradiation therapy (CCRT) regimen using cisplatin and 5-FU followed by adjuvant chemotherapy (AC) in patients with locoregioanlly advanced NPC.

Methods

Forty-three NPC patients who had AJCC stage T3/T4 or N2/N3 and M0 disease were evaluated. The chemotherapy during CCRT consisted of cisplatin (75 mg/m² on day 1) plus 5-FU (750 mg/m²/day on day 1–5), delivered every 4 weeks for two cycles. Three cycles of AC were given with cisplatin (75 mg/m²), epirubicin (37.5 mg/m²) on day 1, and bleomycin (7.5 mg/m² bolus iv. on day 1 followed by 9 mg/m² on day 1–5 by continuous infusion) every 3 weeks.

Results

The overall response rate after CCRT was 95% (22 CRs and 19 PRs in 43) and 100% (16 CRs and 8 PRs in 24) after AC. Grade 3/4 neutropenia, mucositis, and weight loss were observed during CCRT phase in 18, 44, and 26% of patients, respectively. AC caused grade 3/4 neutropenia and emesis in 12.5 and 20.8% of patients, respectively.

Conclusions

CCRT regimen using cisplatin and 5-FU followed by three cycles of BEC chemotherapy was effective in locally advanced NPC patients, with acceptable and reversible acute toxicities.     

Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study)

Background:

The conventional treatment options for advanced gastric patients remain unsatisfactory in terms of response rate, response duration, toxicity, and overall survival benefit. The purpose of this phase II study was to evaluate the activity and safety of cetuximab combined with cisplatin and docetaxel as a first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma.

Methods:

Untreated patients with histologically confirmed advanced gastric or gastro-oesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg m⁻² i.v. followed by weekly doses of 250 mg m⁻², cisplatin 75 mg m⁻² i.v. on day 1, docetaxel 75 mg m⁻² i.v. on day 1, every 3 weeks, for a maximum of 6 cycles, and then cetuximab maintenance treatment was allowed in patients with a complete response, partial response, or stable disease.

Results:

Seventy-two patients (stomach 81.9% and gastro-oesophageal junction 18.1%; locally advanced disease 4.2%; and metastatic disease 95.8%) were enrolled. The ORR was 41.2% (95% CI, 29.5–52.9). Median time to progression was 5 months (95% CI, 3.7–5.4). Median survival time was 9 months (95% CI, 7–11). The most frequent grades 3–4 toxicity was neutropenia (44.4%). No toxic death was observed.

Conclusions:

The addition of cetuximab to the cisplatin/docetaxel regimen improved the ORR of the cisplatin/docetaxel doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS. The toxicity of cisplatin/docetaxel chemotherapy was not affected by the addition of cetuximab.     

Acute toxicity of cyclooxygenase-2 inhibitor rofecoxib as a radiosensitizer for concurrent chemoradiation in the treatment of uterine cervical cancer

Objective

To evaluate the acute toxicity of rofecoxib during concurrent use with cisplatin-based chemoradiotherapy (CCRT) in patients with cervical cancer.

Methods

We evaluated 67 FIGO stage IB2-IVA cervical cancer patients treated with CCRT between June 2002 and July 2004. The study group included patients who received rofecoxib (N=30) and the control group included patients who received CCRT only (N=37). The patients'' medical records were retrospectively reviewed for patient characteristics, toxicity related to CCRT and treatment results.

Results

There were no significant differences in toxicity between the two groups. The most common acute grade 3/4 toxicity was neutropenia (13.3% in the study group and 21.6% in the control group). Grade 3/4 late toxicity was observed in 2 (6.6%) patients in the study group and 3 (8.1%) in the control group. There was no treatment-related deaths in either group. Six (20.0%) patients in the study group had treatment failure. In the control group, 6 (16.2%) patients experienced treatment failure. Progression-free and overall survival was 55.8±4.2 and 59.0±2.8 months, respectively, in the study group, and 69.7±4.3 and 71.6±3.6 months, respectively, in the control group. There were no differences in progression-free and overall survival between the 2 groups.

Conclusion

Our data indicate that rofecoxib, at a dose of 25 mg twice daily, has acceptable acute toxicity as a radiosensitizer during CCRT. Although rofecoxib was not efficacious as a radiosensitizer in the present study, the benefit of rofecoxib as a radiosensitizer should be further evaluated in a prospective study.     

Preoperative Cetuximab,Irinotecan, Cisplatin,and Radiation Therapy for Patients With Locally Advanced Esophageal Cancer

Purpose.

To determine the efficacy and toxicity of weekly neoadjuvant cetuximab combined with irinotecan, cisplatin, and radiation therapy in patients with locally advanced esophageal or gastroesophageal junction cancer.

Methods and Materials.

Patients with stage IIA–IVA esophageal or gastroesophageal junction cancer were enrolled in a Simon''s two-stage phase II study. Patients received weekly cetuximab on weeks 0–8 and irinotecan and cisplatin on weeks 1, 2, 4, and 5, with concurrent radiotherapy (50.4 Gy on weeks 1–6), followed by surgical resection.

Results.

In the first stage, 17 patients were enrolled, 16 of whom had adenocarcinoma. Because of a low pathologic complete response (pCR) rate in this cohort, the trial was discontinued for patients with adenocarcinoma but squamous cell carcinoma patients continued to be enrolled; two additional patients were enrolled before the study was closed as a result of poor accrual. Of the 19 patients enrolled, 18 patients proceeded to surgery, and 16 patients underwent an R0 resection. Three patients (16%) had a pCR. The median progression-free survival interval was 10 months, and the median overall survival duration was 31 months. Severe neutropenia occurred in 47% of patients, and severe diarrhea occurred in 47% of patients. One patient died preoperatively from sepsis, and one patient died prior to hospital discharge following surgical resection.

Conclusions.

This schedule of cetuximab in combination with irinotecan, cisplatin, and radiation therapy was toxic and did not achieve a sufficient pCR rate in patients with localized esophageal adenocarcinoma to undergo further evaluation.     

Comparative study of neoadjuvant chemotherapy before radical hysterectomy and radical surgery alone in stage IB2-IIA bulky cervical cancer

Objective

To compare the efficacy of neoadjuvant chemotherapy with paclitaxel plus platinum followed by radical hysterectomy with radical surgery alone in patients with stage IB2-IIA bulky cervical cancer.

Methods

From November 1999 to September 2007, stage IB2-IIA cervical cancers with tumor diameter >4 cm, as measured by MRI, were managed with two cycles of preoperative paclitaxel and platinum. As a control group, we selected 35 patients treated with radical surgery alone.

Results

There were no significant between group differences in age, tumor size, FIGO stage, level of SCC Ag, histopathologic type and grade. Operating time, estimated blood loss, the number of lymph nodes yielded and the rate of complications were similar in the two groups. In surgical specimens, lymph-vascular space invasion (LVSI), nodal metastasis and parametrial involvement did not differ significantly between the two groups. In the neoadjuvant group, pathologic tumor size was significantly smaller and fewer patients had deep cervical invasion. Radiotherapy, alone and in the form of concurrent chemoradiation, was administered to more patients treated with radical surgery alone (82.9% vs. 52.9%, p=0.006). No recurrence was observed in patients who could avoid adjuvant radiotherapy owing to improved risk factors after neoadjuvant chemotherapy. There were no significant differences in 5-year disease free and overall survival.

Conclusion

As neoadjuvant chemotherapy would improve pathologic prognostic factors, adjuvant radiotherapy can be avoided, without worsening the prognosis, in patients with locally advanced bulky cervical cancer. Neoadjuvant chemotherapy would be improving the quality of life after radical hysterectomy in patients with bulky cervical cancer.     

Cost-utility analysis of treatments for stage IB cervical cancer

Objective

To analyze the cost-utility of two common clinical practices for stage IB cervical cancer patients from provider and societal viewpoints.

Methods

A decision tree model was conducted to examine value for expenditure between the following: (1) radical hysterectomy with pelvic lymph node dissection (RHPLND) with or without postoperative adjuvant therapy according to the risk of recurrence and (2) concurrent chemoradiotherapy (CCRT). The relevant studies were identified to extract the probability data, and meta-analysis was performed. Direct medical costs were estimated from hospital database and medical records review. Direct non-medical costs and utility parameters were obtained through interviews with patients to estimate quality-adjusted life years (QALYs) outcome. The time horizon was according to the life expectancy of Thai women.

Results

From provider viewpoint, RHPLND and CCRT resulted in approximate costs of US $5,281 and US $5,218, respectively. The corresponding costs from societal viewpoint were US $6,533 and US $6,335, respectively. QALYs were 16.40 years for RHPLND and 15.94 years for CCRT. The estimated incremental cost effectiveness ratio of RHPLND in comparison to CCRT from provider and societal viewpoints were US $100/QALY and US $430/QALY, respectively. RHPLND had more cost-effectiveness than CCRT if patients did not need adjuvant therapy. The most effective parameter in model was a direct medical cost of CCRT. At the current ceiling ratio in Thailand, RHPLND provides better value for money than CCRT, with a probability of 75%.

Conclusion

RHPLND is an efficient treatment for stage IB cervical cancer. This advantage is only for patients who require no adjuvant treatment.     

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer

Background:

Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression.

Methods:

Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m⁻², followed by cisplatin 30 mg m⁻² infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m⁻² per day plus leucovorin 90 mg per day on days 1–14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment.

Results:

From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22–75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41–74%) and 53% (95% CI: 38–68%), respectively. The disease control rates in these populations were 85% (95% CI: 70–94%) and 82% (95% CI: 68–92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3–4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities.

Conclusion:

Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.