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PubMed2006

Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: evidence of a radiation and chemotherapy dose response.

BACKGROUND AND PURPOSE: Numerous trials have shown that pathological complete response (pCR) following preoperative chemoradiotherapy (CRT) and surgery for oesophageal cancer is associated with improved survival. However, different radiotherapy doses and fractionations and chemotherapy drugs, doses and scheduling were used, which may account for the differences in observed pCR and survival rates. A dose-response relationship may exist between radiotherapy and chemotherapy dose and pCR. PATIENTS AND METHODS: Trials using a single radiotherapy and chemotherapy regimen (5FU, cisplatin or mitomycin C-based) and providing information on patient numbers, age, resection and pCR rates were eligible. The endpoint used was pCR and the covariates analysed were prescribed radiotherapy dose, radiotherapy dosexdose per fraction, radiotherapy treatment time, prescribed chemotherapy (5FU, cisplatin and mitomycin C) dose and median age of patients within the trial. The model used was a multivariate logistic regression. RESULTS: Twenty-six trials were included (1335 patients) in which 311 patients (24%) achieved pCR. The probability of pCR improved with increasing dose of radiotherapy (P=0.006), 5FU (P=0.003) and cisplatin (P=0.018). Increasing radiotherapy treatment time (P=0.035) and increasing median age (P=0.019) reduced the probability of pCR. The estimated alpha/beta ratio of oesophageal cancer was 4.9 Gy (95% confidence interval (CI) 1.5-17 Gy) and the estimated radiotherapy dose lost per day was 0.59 Gy (95% CI 0.18-0.99 Gy). One gram per square metre of 5FU was estimated to be equivalent to 1.9 Gy (95% CI 0.8-5.2 Gy) of radiation and 100mg/m2 of cisplatin was estimated to be equivalent to 7.2 Gy (95% CI 2.1-28 Gy). Mitomycin C dose did not appear to influence pCR rates (P=0.60). CONCLUSIONS: There was evidence of a dose-response relationship between increasing protocol prescribed radiotherapy, 5FU and cisplatin dose and pCR. Additional significant factors were radiotherapy treatment time and median age of patients within the trial.

Chemotherapy, Adjuvant↗
PubMed2002

Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer: a phase II study by the Hellenic Cooperative Oncology Group.

BACKGROUND: To determine the activity and safety of the combination of paclitaxel and pegylated liposomal doxorubicin (Caelyx) in patients with locally advanced breast cancer. PATIENTS AND METHODS: This was a multicenter phase II study. Thirty-five newly diagnosed patients with locally advanced breast cancer were included in the study. Histological or cytological diagnosis was necessary for inclusion. Median age was 54 years (range 26-73 years). Fifteen patients were premenopausal and 20 postmenopausal. Paclitaxel was administered at a dose of 175 mg/m(2) and pegylated liposomal doxorubicin 35 mg/m(2) every 3 weeks for six cycles. RESULTS: Twenty-five patients (71%) responded. Six (17%) had a complete response, 19 (54%) had a partial response, four remained stable, two progressed and four were not evaluated for response due to discontinuation of chemotherapy. Three patients had a pathologically complete response. A total of 173 cycles were administered. The primary toxicity observed was skin toxicity. Grade 3 skin toxicity was noted in four patients (11%). Palmar-plantar erythrodysesthesia (PPE) grade 3 was experienced by three (9%). Two patients presented with PPE and skin toxicity. Hematological toxicities included grade 3 leukopenia in four patients (3%). Other grade 3 toxicities were uncommon and included only alopecia in 29 patients (83%). Grade 3 or 4 neurotoxicity was not observed in any patient. Dose reduction was necessary in seven patients; in six due to skin toxicity and in one due to neutropenia. Four patients discontinued treatment due to skin toxicity. There were no treatment-related deaths. CONCLUSIONS: The combination of pegylated liposomal doxorubicin and paclitaxel was active in locally advanced breast cancer. The primary toxicity was cutaneous toxicity and it was manageable.

Adult↗
PubMed2005

Complete response following preoperative chemotherapy for resectable non-small cell lung cancer: accuracy of clinical assessment using the French trial database.

BACKGROUND: Pathologic complete response (CR) to preoperative chemotherapy has been shown to be a strong prognostic factor in resected non-small cell lung cancer (NSCLC). This preoperative setting offers the opportunity to evaluate the clinical prediction of CR by investigators and an evaluation committee (EC) using the "gold standard" pathologic examination as the reference. The only published large randomized trial of preoperative chemotherapy (to our knowledge), the French neoadjuvant study, constitutes an interesting database to evaluate CT scan-based CR assessment. STUDY OBJECTIVES AND DESIGN: The French trial compared mitomycin-ifosfamide-cisplatin followed by surgery with surgery alone in stage I (except T1N0) to IIIa resectable NSCLC. Response was prospectively assessed in all patients receiving preoperative chemotherapy by the investigator in charge of the patient and by an EC, and was compared with pathologic postoperative data. RESULTS: In the preoperative chemotherapy study, 167 patients were operated on. Nineteen patients were found to have a pathologic CR. Only seven patients were classified as having a CR by investigators and five patients by the EC. Evaluation of CR was correct in six of these seven cases and in three of these five cases, respectively. Sensitivity of the CR diagnosis was 31.6% for investigators and 15.8% for the EC. Specificities of the CR diagnosis were 99.4% and 98.8%, respectively. Positive predictive values were 85.7% and 60%, respectively. Negative predictive values were 91.9% and 90.1%, respectively. Accuracies were 91.6% and 89.2%, respectively. CONCLUSION: Investigator assessment of CR was highly predictive of pathologic CR. However, this study showed that clinical CT scan-based assessment, whether performed by investigators or the EC, underestimated the frequency of CR after preoperative chemotherapy in resectable NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

The effectiveness of planned esophagectomy after neoadjuvant chemoradiotherapy for advanced esophageal carcinomas.

BACKGROUND: The best treatment option for patients with locally advanced esophageal carcinoma has not yet been determined, especially because the benefits of esophagectomy after neoadjuvant chemoradiotherapy are still controversial. We report the results of a retrospective cohort comparison of definitive chemoradiotherapy without surgery (CRT) versus neoadjuvant chemoradiotherapy followed by planned surgery (CRTS) in patients with advanced esophageal squamous cell carcinoma (SCC). MATERIALS AND METHODS: Between January 1991 and December 2002, 67 patients were enrolled in this study. Fifty of the 67 patients were considered to have inoperable tumors due to distant organ metastasis, distant lymph node metastasis, severe organ dysfunction or rejection of surgery by the patient and received CRT, while the remaining 17 patients were treated with CRTS. The clinical responses of the primary tumors were evaluated. RESULTS: In the 50 CRT patients, the one- and 2-year survival rates were 33.8% and 20.2%, respectively, and the median survival time (MST) was 13.5 months. In the 17 CRTS patients, the response rate (CR + PR) was 76.5%, and the pathological complete response (pCR) rate was 29.4%. Their one- and 2-year survival rates were 61.6% and 35.9%, respectively, and the MST was 24.4 months. The survival rates of the CRT patients were lower than those of the CRTS patients (p = 0.1288). When the 12 patients with distant organ metastases were removed from the CRT group, the one- and 2-year survival rates of the remaining 38 patients were 36.5% and 24.1%, respectively, and the MST was 14.7 months. The survival rates of these 38 CRT patients without distant organ metastases were similar to those of the 12 CRTS patients in the pathological partial response (pPR) group (p = 0.6279). CONCLUSION: This retrospective cohort comparison of CRT versus CRTS demonstrated that there may not be any survival benefit from the addition of surgery in the pPR group for advanced esophageal carcinomas. For patients with a poor response to neoadjuvant chemoradiotherapy, we suggest that the addition of chemoradiotherapy, instead of planned esophagectomy, may show a similar survival rate to definitive CRT. Thus, a large series of a randomized control study will be required to confirm the benefit of surgery after chemoradiotherapy.

Adult↗
PubMed1986

Treatment of locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery.

Fifty-one patients with stage IIIA or IIIB locally advanced breast cancer received primary induction chemotherapy (hormonal synchronization, 46 patients) to a maximum objective clinical response before proceeding to local therapy. Patients achieving a pathological complete response (CR) received radiation therapy, while patients with residual disease, partial response (PR), or stable disease (NC) received debulking surgery prior to radiation therapy; in all patients, 6 additional months of chemotherapy were administered. Chemotherapy consisted of cyclophosphamide (500 mg/m2 iv) and doxorubicin (30 mg/m2 iv) on day 1; tamoxifen (40 mg/m2 orally) on days 2-6; Premarin (0.625 mg/m2 orally) every 12 hours for three doses, beginning on day 7; and methotrexate (300 mg/m2 iv) followed in 1 hour by 5-fluorouracil (500 mg/m2 iv) on day 8 and leucovorin rescue (10 mg/m2 orally) every 6 hours for six doses, beginning 24 hours after methotrexate. Fifty patients are evaluable with respect to response, time to disease progression, and survival. The rate of objective response to chemotherapy was 90%; 52% of the patients had CR, 38% had PR, and 10% had NC. The median numbers of chemotherapy cycles to achieve CR, PR, and NC were five, four, and four, respectively. Twenty-four patients with CR to chemotherapy were pathologically assessed, 22 by multiple biopsies and 2 by mastectomy. Seventy-one percent of the patients were proven to have pathological CR. All patients completing combined therapy thus far are disease free. Nine of 29 patients with stage IIIB disease have relapsed; 7 of 23 with inflammatory histology have relapsed; and 2 of 20 with stage IIIA disease have relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

BACKGROUND: [F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. METHODS: Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. RESULTS: The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. CONCLUSIONS: In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Animals↗
PubMed2001

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.

Adenocarcinoma↗
PubMed2000

Preoperative ECF chemotherapy in gastro-oesophageal adenocarcinoma.

Epirubicin, cisplatin and continuous 5-fluorouracil (5-FU) infusion (ECF) has been reported to result in high clinical response rates in advanced gastro-oesophageal adenocarcinoma and is currently the 'gold standard' chemotherapy regimen for this tumour site. Despite this, its role as preoperative (neoadjuvant) treatment is unproven and therefore remains under investigation. We report our experience using ECF (intravenous epirubicin 50 mg/m2 and cisplatin 60 mg/m2 every 3 weeks, with continuous infusion of 5-FU 200 mg/m2 per day) as preoperative treatment in locally advanced adenocarcinoma of the lower oesophagus, gastro-oesophageal junction and stomach. Of the 23 patients treated (median age 54 years), 19 had potentially resectable disease, four were unresectable and seven had radiological evidence of lymph node involvement. A median of four cycles of ECF was delivered (range 1-6). Ten of 12 patients (83%) with dysphagia reported improvement of symptoms. Clinical disease progression occurred in six patients (26%) during chemotherapy. WHO grade 3 or 4 toxicity occurred in six patients (26%): four haematological, one mucositis, one vomiting. Seventeen patients (74%) proceeded to surgery; 14 (61%) were resected and three were unresectable. There were two (12%) postoperative deaths from respiratory failure. Major pathological response was seen in three patients (13%): one pathological complete response, two microscopic residual disease. Two patients had Stage II (T2N(0-1)) disease and nine were Stage III (T(3-4)N(0-1)). None of the patients with initially unresectable disease was rendered resectable. After a median follow-up interval of 33 months (range 26-53), the overall median survival was 12 months and 2-year survival was 30%. All patients who were initially unresectable or had radiological evidence of lymph node involvement have died. Therefore, despite good symptomatic response rates, ECF chemotherapy given in the preoperative setting did not appear to improve the outcome of patients with unresectable or radiologically lymph node-positive gastro-oesophageal adenocarcinoma. The role of ECF chemotherapy in resectable tumours is unclear and is currently under investigation in the randomized MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) study.

Adenocarcinoma↗
PubMed2004

Pathologic changes in breast cancer following neoadjuvant chemotherapy: implications for the assessment of response.

Neoadjuvant chemotherapy (also known as preoperative or primary chemotherapy) is the treatment of choice for patients with locally advanced breast cancer. One of the main advantages of neoadjuvant chemotherapy is that it allows for assessment of pathologic response to treatment. Clinical and radiologic evaluations of response to neoadjuvant chemotherapy are based on change in tumor size, and the correlation with pathologic response is often inaccurate. Pathologic evaluation of tumor size remains the gold standard for evaluation of residual tumor after chemotherapy. Chemotherapy-induced histomorphologic change is commonly observed in posttreatment resection specimens and can contribute to the less-than-perfect correlation between the clinical assessment of tumor size and the pathologic measurement. Therefore, accurate histologic mapping to the macroscopic and radiologic appearance of the tumor bed is necessary. Cytopathologic changes are also common in residual cancer cells after neoadjuvant chemotherapy and have uncertain clinical relevance. There is a role for the development of new histologic approaches to augment the pathologic and clinical assessment and provide information on the differential response, particularly for tumors in which less than pathologic complete response is achieved.

Breast Neoplasms↗
PubMed1990

[Ovarian carcinoma: current therapeutic aspects. A review].

Ovarian cancer is the leading cause of gynaecologic cancer death and the fourth most frequent cause of cancer death in women. 70% of all ovarian cancers will be diagnosed only at an advanced stage of the disease despite the improvements in diagnostic tools. Standard therapeutic concepts and new therapeutic modalities are discussed. Staging laparotomy with cytoreductive surgery is the most important part of initial patient management. Second-look operation has recently come under criticism, as it probably offers only minor therapeutic benefit. However, it remains the golden rule for evaluating different therapy modalities in the setting of a clinical trial. After surgery, chemotherapy is indicated for all patients with ovarian cancer FIGO stage III and IV. The question whether all patients with stage I and II disease need additional treatment remains unresolved. The standard regimen for patients with advanced ovarian cancer consists of six months' chemotherapy with a combination of cisplatin and an alkylating agent. Current cisplatin containing regimens achieve a clinical response rate of 60-80% and a documented pathologic complete response rate of 30% overall. Despite higher overall response rates and increased disease-free survival rates with cisplatinum combinations, long term survival is not significantly altered. Investigative approaches with intraperitoneal chemotherapy, biologic response modifiers and drug resistance modifiers may open new therapeutic avenues for this challenging disease. Radiotherapy (open field technique) also represents a highly active and curative treatment modality for certain ovarian cancer patients. Nowadays radiotherapy is mainly used as adjuvant treatment for patients with low risk early stage disease and as consolidation treatment for patients with complete remission after chemotherapy and second-look operation.

Adult↗
PubMed1994

Carboplatin and alpha-2b interferon intraperitoneal combination as first-line treatment of minimal residual ovarian cancer. A pilot study.

21 untreated ovarian cancer patients with stage III and minimal tumour size, were given weekly intraperitoneal (i.p.) carboplatin (150 mg/m2) and alpha-2b interferon (IFN) (30 million U/m2) for a total of 12 courses, from June 1989 to February 1993. To date, a total of 248 courses have been administered. Toxicity was seldom severe, although fever (179 courses), fatigue (141 courses) and other IFN-related side-effects were very frequent. No patient refused to continue treatment, but in 5 patients IFN dose had to be reduced, and in 1 it was discontinued. The IFN mean delivered dose intensity was 19.8 million U/m2 week. Grade 3-4 myelotoxicity occurred in 7 patients (39 courses), but no deaths related to treatment occurred. The actual mean dose intensity of carboplatin was 121.5 mg/m2 week. To date, 20 patients have completed treatment and are evaluable for response. Of 11 patients with tumour size < or = 5 mm, 10 (91%) achieved a pathological complete response (pCR) as did 4/9 (44%) of those with tumour > 5 mm at entry, for a 70% (95% confidence interval 50-90) overall pCR rate. At a median follow-up of 21 months (range 4-46), only one death occurred. The probability of being alive at almost 4 years was 91% in the entire group (100% in those with tumour size less than 5 mm). Only 1 of 14 patients who achieved a pCR relapsed. This i.p. combination seems a feasible approach to previously untreated ovarian cancer patients with minimal tumour burden. IFN dosage should be reduced to improve tolerance. In view of the very high pCR rate achieved in the group of patients with smaller tumours, a randomised trial is warranted to compare this approach to standard treatment in these patients.

Adult↗
PubMedDate not supplied

Efficacy and toxicity of nedaplatin and 5-FU with radiation treatment for advanced esophageal carcinomas.

BACKGROUND: Nedaplatin, a new analog of cisplatin, has been developed and marketed in recent years in Japan. In this study, we evaluated the efficacy and toxicity of a regimen of nedaplatin and 5-FU with radiation in patients with advanced esophageal carcinomas. MATERIALS AND METHODS: Between June 1999 and December 2002, 42 patients with advanced and unresectable thoracic esophageal squamous cell carcinomas (SCCs) were enrolled into this study. Twenty-five of these 42 patients were considered to have inoperable tumors due to distant organ metastasis, distant lymph node metastasis, severe organ dysfunction and rejection of surgery by the patients. The remaining 17 patients received neoadjuvant treatment followed by surgery. The clinical responses of the primary tumors were evaluated. RESULTS: Response and toxicity could be assessed in 22 of the 25 patients with unresectable esophageal SCCs. Two of these 22 achieved a complete response (CR), 15 had a partial response (PR) and 5 showed no change (NC). The overall response rate (CR + PR) was 77%. The one- and 2-year survival rates were 30.7% and 10.2%, respectively, with a median survival time (MST) of 10.1 months. Of the 17 patients who received neoadjuvant treatment, 14 underwent subsequent surgery. Preoperatively, 2 of these 17 patients achieved a CR, 10 had a PR and 5 showed NC. The overall response rate for all 39 patients was 74%. The pathological complete response (pCR) rate of the 14 patients who underwent surgery was 28.6%. Their one- and 2-year survival rates were 48.2% and 12.1%, respectively, with an MST of 12.2 months. Toxicity was evaluated in the 39 patients whose responses were assessed. Toxicity higher than grade 3 occurred in 8 out of 39 (20.5%) patients, and 6 (15.4%), 3 (7.7%) and one (2.6%) had grade 3 leukopenia, thrombocytopenia and anemia, respectively. CONCLUSION: In conclusion, this study indicates that combination chemoradiotherapy with nedaplatin and 5-FU is safe and efficacious for patients with advanced esophageal carcinomas. We recommend further evaluation of this treatment regimen in such patients.

Adult↗
PubMed2005

Unique gene expression profile based on pathologic response in epithelial ovarian cancer.

PURPOSE: We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients. RESULTS: A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set, the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX, a proapoptotic protein previously associated with chemotherapy response in ovarian cancer. CONCLUSION: Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway.

Adenocarcinoma, Clear Cell↗
PubMed1997

Ifosfamide plus cisplatin as primary chemotherapy of advanced ovarian cancer.

We have performed a phase II study to evaluate the activity and toxicity of ifosfamide and cisplatin as first-line treatment for advanced ovarian cancer. Patients were treated with cisplatin 100 mg/m2 on day 1 and ifosfamide 5 g/m2 in 18-hr continuous infusion on day 1 or 1.5 g/m2 bolus on days 1-5. Between August 1988 and March 1990, 30 women were entered in the trial, 26 of them with measurable disease. The overall clinical response rate was 69% (95% CI: 48-85%), including 34.6% complete responses (95% CI:17-55%). Reassessment laparotomy was performed in 12 cases, and 4 (33%) exhibited a pathologic complete response. For all patients, the median duration of progression-free survival was 14 months, and the median overall survival was 25 months. There were no major differences in the response rate or survival between the two ifosfamide administration modalities. Relevant toxicities were grade IV hematologic toxicity in 11/30 patients and grade IV renal toxicity in 2/30 patients. A patient with grade IV encephalopathy developed a trauma-related cerebral hemorrhage and died 2 months later. The combination of ifosfamide and cisplatin is active in first-line therapy in advanced ovarian cancer, although it does not seem to improve the efficacy or toxicity profile of conventional combinations.

Adult↗
PubMed1996

Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma.

To prospectively evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy locally advanced or recurrent vulvar carcinoma, 58 patients referring for primary (41) or recurrent (17) disease received preoperative external radiotherapy to a dose of 54 Gy, divided into two courses with an interval of 2 weeks. 5-Fluorouracil (750 mg/m2 daily for 5 days) and mitomycin-C (15 mg/m2 single bolus) were given at the start of each cycle. Wide local excision and inguinal lymphadenectomy were planned after treatment. Eighty-nine percent of patients completed the chemoradiotherapeutic treatment, whereas 72% underwent surgery. Objective responses were observed in 80% of vulvar diseases and in 79% of groin metastases. Pathologic complete response of both the vulvar and inguinal disease was confirmed in 13 patients (31%). Early severe toxicity was recorded in 3 patients and severe worsening of performance status in 3. Three deaths occurred shortly after treatment and at least one is directly related to toxic effects. This treatment allows good control of locally advanced and recurrent vulvar cancer with acceptable side effects. Further follow-up is required to determine the long-term outcome and the effectiveness of the surgical procedure.

Antibiotics, Antineoplastic↗
PubMed2005

Radiochemotherapy in the management of pancreatic cancer--part I: neoadjuvant treatment.

In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alone are suboptimal. Many studies have been conducted in which the treatment regimen consists of surgery in combination with radiation and chemotherapy to improve local control and outcome. Neoadjuvant chemoradiotherapy is a fairly recent approach that appears to be feasible in resectable and locally advanced pancreatic cancer. In resectable tumors, chemoradiation therapy has been shown to be at least as effective in a neoadjuvant setting as in an adjuvant setting. Neoadjuvant therapy offers a few theoretical advantages: (1) beginning the multimodality treatment with chemoradiation therapy increases the chance that more patients will receive all of its components; (2) preoperative chemoradiation therapy provides an observation period to exclude from surgical resection those patients with rapidly progressive disease; and (3) in locally advanced tumors, it provides the opportunity for downstaging and infrequently allows patients to undergo resection. To evaluate the scope and applicability of neoadjuvant treatment, a number of areas need to be addressed. First, the definition of locally advanced disease needs to be more adequately standardized because the resectability definition sometimes varies among surgeons. In addition, because imaging examinations may underestimate the effectiveness of preoperative chemoradiation therapy, some researchers have tried to evaluate treatment response via a pathological examination of the tumor specimen; however, complete pathological response appears to be rare. Finally, more efficient novel neoadjuvant approaches are required to address the high metastatic potential of pancreatic cancer. These areas are discussed in depth.

Adenocarcinoma↗
PubMed2006

Phase II study of preoperative paclitaxel/cisplatin with radiotherapy in locally advanced esophageal cancer.

PURPOSE: Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival. METHODS AND MATERIALS: Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m2 on Day 1 and 5-fluorouracil 350 mg/m2 and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy. RESULTS: Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p < 0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%. CONCLUSION: Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.

Adenocarcinoma↗
PubMed2005

Correlation between histological effects on the main tumors and nodal status after chemoradiotherapy for squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Although the histological effectiveness of preoperative chemoradiotherapy against the main tumor is reported to be the strongest prognostic factor for patients with esophageal cancer, it remains unknown whether such chemoradiotherapy is equally effective against metastatic lymph nodes. METHODS: We studied 103 consecutive patients with esophageal cancer, who were given preoperative chemoradiotherapy followed by surgery. The histological effectiveness against the main tumor of the chemoradiotherapy was correlated with lymph mode metastasis and other clinico-pathological factors. RESULTS: The histological effectiveness against the main tumor was grade 3 in 26 patients, grade 2 in 49 and grade 1 in 28. The number of pathological node-negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade 3, 2, and 1 responses of their main tumors, respectively. The average number of pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade 3, 2, and 1 responses, respectively. Endoscopic biopsy after the chemoradiotherapy could not accurately diagnose the pathological complete response (CR) of the main tumors, with a high false negative rate (60.9%). CONCLUSIONS: The effects of chemoradiotherapy against main tumors significantly correlated with nodal status. Most patients with main tumors of pathological CR are node-negative. Patients with a grade 2 response have at most a few positive nodes. Surgery would be most beneficial for such patients.

Adult↗