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PubMed2006

Update on capecitabine in colorectal cancer.

In combination chemotherapy for metastatic colorectal cancer, i.v. 5-fluorouracil (5-FU) can be replaced by oral 5-FU (in the form of capecitabine or another orally available analogue) without negatively affecting overall toxicity and without remarkably reducing the efficacy of treatment in terms of response rate or overall survival. Preclinical evidence of synergy has led to promising early and successfully completed studies combining capecitabine plus oxaliplatin with bevacizumab, cetuximab, and epidermal growth factor receptor tyrosine kinase inhibitors. The use of preoperative capecitabine plus radiation is achieving good rates of pathological complete response in rectal cancer. While capecitabine is generally well tolerated, its potential toxicities need careful management and may require individual dose adaption.

Antimetabolites, Antineoplastic↗

PubMed1992

Prolonged chemotherapy for localised squamous carcinoma of the oesophagus.

We evaluated the feasibility of six courses of chemotherapy in 34 consecutive patients with localised squamous cell carcinoma of the oesophagus. All 32 evaluable patients first received at least two courses of chemotherapy. There were 18 patients with resectable carcinomas who underwent surgery and 14 patients with unresectable carcinomas who received definitive chemoradiotherapy. After two courses of 5-fluorouracil and cisplatin 21 (66%) of 32 patients had either a complete or major response. A median of five courses (range, 1-6 courses) was administered. 17 out of 18 (94%) patients with resectable carcinoma had a 'curative' resection (negative proximal, distal, and radial margins by histopathology in an en-block resection specimen) and 2 patients had a complete pathological response. The median survival duration of all patients was 28 months (range, 2-46+ months). The median survival duration of 14 patients with unresectable carcinoma was 23 months (range, 8-36+ months), and the median survival duration of 18 patients with resectable carcinoma has not been reached at a median follow-up of 24+ months (range, 10+ to 46+ months). No deaths occurred because of chemotherapy or chemoradiation therapy. Our data suggest that prolonged chemotherapy is feasible in patients with locoregional squamous carcinoma of the oesophagus. An ongoing controlled trial will determine the contribution of chemotherapy to patients' survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Postmastectomy morbidity after combination preoperative irradiation and chemotherapy for locally advanced breast cancer.

Neoadjuvant therapy for locally advanced breast cancer improves disease control, but the complications of treatment are not well established. The aim of this study was to assess the operative morbidity in 20 consecutive patients with locally advanced, noninflammatory breast cancer treated with preoperative chemotherapy and radiation. Patients received preoperative cyclophosphamide, methotrexate, 5-fluorouracil, prednisone, and tamoxifen (CMFPT) to maximum response followed by concurrent chemotherapy and radiation to the involved breast and regional lymph nodes. Following modified radical mastectomy, chemotherapy was continued for a total of 10 cycles. Disease progressed in 3 of 20 patients (15%). Seventeen patients underwent mastectomy, 4 (24%) of whom demonstrated a pathologic complete response to chemoradiotherapy. Seven patients (41%) developed wound infections, 2 (12%) necrosis, 5 (29%) delayed healing, 2 (12%) upper extremity lymphedema, and 8 (47%) seromas. Postoperative chemotherapy was delayed in 4 (24%) patients. There was no mortality, and hospitalization was for less than 1 week. Only one patient required readmission. Although this treatment regimen is aggressive with attendant morbidity, complications are easily managed and generally do not delay therapy. Treatment modification to further reduce complications may be indicated.

Adult↗

PubMed2006

Examining the need for neck dissection in the era of chemoradiation therapy for advanced head and neck cancer.

OBJECTIVES: To (1) determine clinical factors that predict pathologic complete response (pCR) on neck dissection after sequential chemoradiotherapy (SCRT) for advanced head and neck cancer and (2) compare survival parameters between those who underwent neck dissection and those who did not among those patients with a clinical complete response (cCR) in the neck after SCRT, thus assessing the benefit of neck dissection in patients with a cCR in the neck. DESIGN: Retrospective review with a mean follow-up of 3.5 years. SETTING: Regional cancer center. PATIENTS: The study population comprised 55 patients undergoing SCRT for advanced head and neck cancer with N2 or N3 neck disease. Three patients developed progressive disease and were excluded, and 28 patients underwent neck dissection. INTERVENTIONS: Patients were assessed by physical examination and radiographically after SCRT. MAIN OUTCOME MEASURES: Physical examination and radiographic assessments of residual neck disease were compared with pathologic findings in those patients who underwent neck dissection. Survival comparisons were made between patients with a cCR in the neck who underwent neck dissection and those who did not. RESULTS: Of 28 patients who underwent neck dissection, 8 had persistent pathologically positive nodal disease: 5 (45%) of 11 had N3 and 3 (18%) of 17 had N2 disease. Individual clinical neck assessments after SCRT were fairly predictive of a negative pathologic finding at neck dissection. The negative predictive values were physical examination (75%), computed tomography or magnetic resonance imaging (71%), and positron emission tomography (75%). However, when physical examination, imaging studies, and positron emission tomography all indicated a complete response, this accurately predicted a pCR on neck dissection. There appeared to be no improvement in survival parameters when a neck dissection was performed on patients with a cCR in the neck. CONCLUSIONS: Patients with N3 disease are at high risk for residual neck metastasis after SCRT. Patients with N2 disease can be assessed with physical examination, imaging studies, and positron emission tomography. If these all indicate a cCR, then neck dissection is likely not needed. Neck dissection did not appear to further improve survival parameters for patients with a cCR in the neck.

Adult↗

PubMed1999

Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results.

Locoregionally advanced squamous cell carcinomas of the head and neck continue to be a major clinical problem. We demonstrated in 1996 that preoperative concurrent cisplatin- or carboplatin-based chemotherapy and radiotherapy plus radical surgery in advanced oral cancer had minimal toxicity, had high clinical tumor response rates, was well tolerated and produced impressive complete response rates and a high 5-year survival rate. The purpose of the present study was the long-term follow-up of this treatment regimen for advanced oral carcinoma. Forty-eight patients with squamous cell carcinoma of the oral cavity (including soft palate) were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy, and 2-6 weeks later underwent curative surgery. All patients with advanced Stage II (n=7), Stage III (n=22) and Stage IV (n=19) were treated and followed for an average of 7.2 years (range: 61-144 months). The overall actuarial survival of all patients was 81.3% at 5 years and also at 10 years. Progression-free survival at both 5 and 10 years was 84.8% for all patients, and 85.7% for Stage II, 90.0% for Stage III, and 78.9% for Stage IV patients. Progression-free survival rates according to the histopathologic regression grade of primary tumor following preoperative chemoradiotherapy at 10 years were 40. 0% for Grade IIa, 88.9% for Grade IIb, 100% for Grade III, and 87.5% for Grade IV. Patients who achieved good responses histopathologically (Grades IIb, III, IV) had superior survival rates in comparison to patients with extensive residual tumor (Grade IIa) in surgically resected specimens (p=0.0012). A better histologic regression grade was also associated with a higher survival rate even in the long-term analysis. This treatment regimen for advanced oral cancer produced high clinical and pathologic complete response and survival rates with an acceptable acute toxicity profile and lack of late therapeutic complications. The long-term follow-up showed gratifying results even for advanced oral cancers without a substantial increase in distant metastasis and second primary malignancy.

Adult↗

PubMed2005

Paclitaxel, carboplatin and gemcitabine combination as induction chemotherapy for stage IIIA N2 bulky non-small cell lung cancer.

BACKGROUND: Induction chemotherapy followed by surgical resection or definitive radiotherapy for patients affected by stage IIIA N2 bulky non-small cell lung cancer (NSCLC) has been investigated in several trials. PATIENTS AND METHODS: In this present study, 52 patients with stage IIIA N2 bulky NSCLC with cytologically or histologically confirmed mediastinal lymph node involvement received paclitaxel 175 mg/mq on day 1, carboplatin AUC 5 on day 1 and gemcitabine 1,000 mg/mq on day 1 and 8 every 3 weeks for three cycles as induction chemotherapy. RESULTS: Objective response (4 complete remission and 36 partial remission) was achieved in 40/52 patients. No early or toxic deaths were observed. Twenty-two patients were surgically explored. Fifteen were excluded for resection for biopsy-proven residual tumour in mediastinal nodes. Complete surgical resection was performed in 15 patients with confirmed pathological downstaging. Pathological complete response was achieved in 4 patients. No surgery-related mortality or significant morbidity was reported. Adjuvant radiotherapy was delivered in 15 patients, and 30 patients received definitive radiotherapy. CONCLUSION: In the present study, the combination of paclitaxel, carboplatin and gemcitabine has been a safe and active regimen in poor-prognosis stage IIIA N2 bulky NSCLC.

Adult↗

PubMed1998

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

Adenoviridae↗

PubMed1991

A phase I-II trial of intraperitoneal cisplatin and alpha-interferon in patients with persistent epithelial ovarian cancer.

A toxicity, dose, and schedule study of intraperitoneal (ip) cisplatin and alpha-interferon was conducted as a salvage therapy for patients with persistent, advanced epithelial ovarian cancer after primary systemic therapy with cisplatin-combination chemotherapy. Twenty-four patients were entered into this prospective, nonrandomized phase I-II trial conducted at two institutions following a uniform protocol. Cisplatin doses were escalated from 45 to 90 mg/m2, and alpha-interferon doses were escalated from 10 to 50 x 10(6) IU. At protocol entry, 4 (16%) patients had microscopic residual disease at second-look laparotomy, 5 (21%) had minimal residual disease less than 5 mm, 7 (30%) had residual disease 5-20 mm, and 8 (33%) had bulky residual disease greater than 20 mm. Toxicity was acceptable overall. Hematopoietic toxicity included a grade 3 total white cell count in 12% of courses when the cisplatin dose was equal to or greater than 60 mg/m2. Renal toxicity was modest with grade 2 toxicity in 20% of courses with a cisplatin dose greater than 60 mg/m2. Gastrointestinal toxicity, especially nausea and vomiting was seen in most courses; however, it was grade 3 and dose-limiting in greater than 30% of courses with cisplatin 75-90 mg/m2. General malaise, fever, flu-like symptoms, chills, and myalgias were seen in most courses, but it was dose-limiting (grade 3) toxicity in 6-11% of cycles when the dose of interferon was 25-50 x 10(6) IU. There was no grade 4 toxicity. Thus, the maximum tolerated dose (MTD) of the combination is 60 mg/m2 cisplatin and 25 x 10(6) IU interferon. Eighteen patients were evaluable for response, 15 of whom had responded to prior cisplatin therapy and 3 had not. Of the 10 patients evaluable for clinical response, one patient (10%) achieved a complete response (CCR), and one (10%) had a partial response (PCR). The progression free interval (PFI) and survival were 11 months and 19 months, respectively, for the CCR patient, 6 and 11 months, respectively, for the PCR patient, and the mean survival for nonresponders was 8 months. The other 8 patients underwent a reassessment laparotomy: 2 (25%) achieved a complete pathologic response (CPR), and 3 (38%) had a partial pathologic response (PPR). Both pathologic responses were in patients with minimal residual disease less than 5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2004

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.

Adenocarcinoma↗

PubMed2005

Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes.

PURPOSE: To investigate the impact of histologic type invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) on response to primary chemotherapy (PC) and long-term outcome. PATIENTS AND METHODS: The study included 1,034 patients with stage II and III breast cancer who participated in six clinical trials of PC at our institution between 1985 and 2002. One hundred twenty-two patients (12%) had ILC and 912 (88%) had IDC. All patients received anthracycline-based PC, and 346 patients (33.5%) also received a taxane as part of PC. Pathologic complete response (pCR) was defined as no evidence of invasive disease in the breast and axillary lymph nodes. RESULTS: The median patient age was 48 years (range, 18 to 79 years). Patients with ILC tended to be older (median age, 53 years v 47 years for patients with IDC) and have more hormone-receptor-positive tumors (92% v 62%; P < .001), lower nuclear grade (nuclear grade 3, 16% v 56%; P < .001), and higher stage at diagnosis (10% v 0% with stage IIIB or IIIC disease; P < .001). Patients with ILC were less likely to have a pCR (3% v 15%; P < .001) and had a larger number of involved axillary lymph nodes (41% v 26% had > 3 involved nodes; P = .001). At a median follow-up time of 70 months, ILC patients tended to have longer recurrence-free survival (P = .004) and overall survival (P = .001). CONCLUSION: ILC is characterized by lower rates of pathologic response to PC but better long-term outcomes compared to IDC. pCR might not be a prognostic indicator for this group of patients.

Adolescent↗

PubMed2004

A preliminary study of preoperative chemotherapy combining irinotecan and cisplatin in patients with gastric cancer with unresectable para-aortic lymph node metastases.

BACKGROUND: A high response rate has been reported for chemotherapy combining irinotecan (CPT-11) and cisplatin (CDDP) against advanced gastric cancer. The strong anti-tumor activity of this regimen makes it very attractive as a preoperative chemotherapy. We conducted a preliminary study on preoperative chemotherapy with this regimen in patients with unresectable gastric cancer with para-aortic lymph node metastases to evaluate the feasibility of it as a treatment strategy. METHODS: Patients with unresectable para-aortic lymph node metastasis without distant hematogenous metastasis (H0, M0 and M1 LYM) and peritoneal dissemination (P0) were eligible for entry. The preoperative chemotherapy consisted of at least three cycles of CPT-11 (70 mg/m(2)) on days 1 and 15 and CDDP (80 mg/m(2)) on day 15, repeated every 4-6 weeks. Chemotherapy was followed by surgery with extended lymph node dissection in patients who achieved complete or partial responses and whose cancers were judged to be resectable. RESULTS: Six patients were entered into the study. In total, 18 cycles of chemotherapy were performed and five patients received at least three cycles. Objective partial responses were achieved in four patients. The major toxicities in the chemotherapy were neutropenia and diarrhea, but these were clinically acceptable. Four patients underwent surgery after the chemotherapy, and macroscopically complete resections with extended lymph node dissection were achieved in two patients. There were no therapy-related deaths. We found no pathological complete responses, but observed a definite histopathological effect caused by the chemotherapy in surgical specimens. The median survival time of all patients was 12 months. The longest survival without relapse is >6 years from the start of therapy. CONCLUSIONS: We conclude that preoperative chemotherapy with CPT-11/CDDP therapy is feasible in patients with advanced gastric cancer and that the regimen is safe when followed by surgery. Further clinical studies with larger numbers of patients are warranted to evaluate the efficacy of this strategy.

Adenocarcinoma↗

PubMed2000

p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma.

PURPOSE: The p53 gene plays a critical role in cellular response to DNA damage and has been implicated in the response to platinum compounds in ovarian carcinoma patients. Because taxanes could induce p53-independent apoptosis, we assessed the relevance of p53 gene status to response in ovarian carcinoma patients receiving paclitaxel and platinum-containing chemotherapy. PATIENTS AND METHODS: Forty-eight previously untreated patients with advanced disease received standard paclitaxel/platinum-based chemotherapy. In tumor specimens collected at the time of initial surgery, before therapy, p53 gene status and expression were examined by single-strand conformation polymorphism, sequence analysis, and immunohistochemical analysis. Microsatellite instability analysis was performed on available samples from 30 patients. RESULTS: Thirty-four (71%) of the 48 patients had a clinical response. Pathologic complete remission was documented in 13 (27%) of 48 patients. p53 mutations were detected in 29 (60%) of 48 tumors. Among the patients with mutant p53 tumors, 25 patients (86%) responded to chemotherapy. Only nine (47%) of 19 patients with wild-type p53 tumors responded to the same treatment. The overall response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than among patients with wild-type p53 tumors (P: =.008). Most of the tested tumors not associated with complete remission (10 of 12 tumors) were also characterized by microsatellite instability. The complete remission rate was higher among patients with tumors without microsatellite instability (five of seven patients). CONCLUSION: In contrast to the limited efficacy of treatment with paclitaxel in combination with standard platinum doses against wild-type p53 ovarian tumors, patients with mutant p53 ovarian tumors were more responsive to paclitaxel-based chemotherapy. The pattern of response to chemotherapy containing paclitaxel is different from that associated with high-dose cisplatin therapy. Determining p53 mutational status can be useful in predicting therapeutic response to drugs effective in ovarian carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Preoperative chemoradiotherapy in cancer of the thoracic esophagus.

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.

Adenocarcinoma↗

PubMedDate not supplied

Neoadjuvant chemo-irradiation in un-resectable carcinoma of rectum.

BACKGROUND: Rectal cancer is one of the most frequent gastrointestinal cancers. Conventionally surgery is the mainstay of treatment, however after surgery alone, local recurrence is high especially in locally advanced rectal cancer, i.e. tethered and fixed rectal cancer. This study was conducted to determine the role of neo-adjuvant (pre-operative) chemoirradiation in locally advanced carcinoma of the rectum to improve resectability, local control and survival. METHODS: Study was conducted in Radiation Oncology department of Shaukat Khanum Memorial Cancer Hospital and Research Center from May 97-Oct 99. Thirteen patients with unresectable/locally advanced adenocarcinoma rectum received neo-adjuvant chemoirradiation, 50 Gray to pelvis by box technique on Cobalt-60 machine with concomitant 5-Flurouracil 500 mg/m2 for first three and last three days followed by abdomino-perineal/low anterior resection. RESULTS: Neo-adjuvant chemoirradiation resulted in resectability rate of 92% and clinical down staging in 11/13 (84%) patients and pathological complete response in 2/13 (15%) patients and a local recurrence rate of 2/13 (15.38%). Non hematological toxicity (diarrhea grade 4--15%, erythema grade 3--23%, dysuria grade 1-2--38%) were main problems observed during neo-adjuvant chemoirradition. CONCLUSION: Concomitant preoperative chemoirradiation for locally advanced rectal cancer is associated with considerable clinical and pathological down staging. Tumor resectability is improved with potential for improved local control and is relatively safe with acceptable morbidity.

Adenocarcinoma↗

PubMed2003

Prospective comparison of 18F-FDG PET with conventional imaging modalities (MRI, CT, and 67Ga scintigraphy) in assessment of combined intraarterial chemotherapy and radiotherapy for head and neck carcinoma.

UNLABELLED: To preserve the oral organs and functions in patients with head and neck carcinoma, accurate determination of the appropriate treatment after neoadjuvant chemotherapy and radiotherapy is of critical importance. We evaluated the diagnostic accuracy of (18)F-FDG PET relative to that of other conventional imaging modalities in the assessment of therapeutic response after combined intraarterial chemotherapy and radiotherapy as an organ preservation protocol. METHODS: The study was prospectively performed on 23 consecutive patients with head and neck squamous cell carcinoma who completed the treatment regimen and underwent 2 (18)F-FDG PET studies before and after neoadjuvant chemoradiotherapy. (67)Ga scintigraphy (only before therapy) as well as MRI and CT (both before and after therapy) were also performed. All images were blindly and independently interpreted without knowledge of histologic findings. The level of confidence in image interpretation was graded by means of a 5-point rating system (0 = definitely no tumor to 4 = definite tumor). RESULTS: Before treatment, (18)F-FDG PET detected primary tumors in all 23 patients and was more sensitive (100%) than MRI (18/23; 78.3%), CT (15/22; 68.2%), and (67)Ga scintigraphy (8/20; 40%), with a confidence level of 3 or 4 as a positive tumor finding. After chemoradiotherapy, residual tumors were histologically confirmed in 4 patients (pathologic complete response rate, 19/23; 82.6%). Although posttreatment (18)F-FDG PET showed almost equal sensitivity (4/4; 100%) compared with MRI (3/3; 100%) or CT (3/4; 75%), its specificity (17/19; 89.5%) was superior to MRI (7/17, 41.2%) and to CT (10/17; 58.8%) for primary lesions. Regarding metastases to neck lymph nodes, only specificity for posttreatment images was calculated because no metastasis was confirmed in any patients after treatment. Six subjects had (18)F-FDG PET-positive lymph nodes, which had pathologically no tumor cells and suggested an inflammatory reactive change after therapy. Therefore, the specificity of posttreatment (18)F-FDG PET (17/23; 73.9%) was almost identical to that of MRI (17/20; 85%) and CT (16/21; 76.2%) for neck metastasis. With combined chemoradiotherapy monitored with (18)F-FDG PET, 8 patients avoided surgery and the remaining 15 patients underwent a reduced form of surgery. CONCLUSION: (18)F-FDG PET facilitates differentiation of residual tumors from treatment-related changes after chemoradiotherapy, which may be occasionally difficult to characterize by anatomic images. (18)F-FDG PET has a clinical impact for the management of patients with head and neck cancers after neoadjuvant chemoradiotherapy by optimizing surgical treatment for each patient and contributes to the improvement of the patient's quality of life.

Aged↗

PubMed2006

[A case report of cancer of the lip--complete response by a neo-adjuvant chemotherapy using a novel method of TS-1 administration].

We experienced a 49-year-old man with cancer of the lower lip (squamous cell carcinoma, T1N2cM0). We planned surgical treatment including bilateral neck dissection and started a new TS-1 administration method as a neo-adjuvant chemotherapy. One course of this chemotherapy consisted of 3 weeks'administration including 5-day administration and 2-day termination following 1 week rest. TS-1 was given at 120 mg/day. After the first course of chemotherapy, the primary tumor disappeared, and the neck lymph node metastases were markedly reduced. There was no obvious side effect except mild stomatitis. Since we assumed that the lymph node palpated in left neck was a residual tumor, we performed left neck dissection. Histopathological examination revealed that there was no cancer cell but hyalinization in the removed specimen of lymph node, suggesting that the effect of the chemotherapy was a pathologically complete response. We concluded that our novel TS-1 administration method was extremely effective for head and neck squamous cell carcinomas with high potential and without any severe side effects.

Antimetabolites, Antineoplastic↗

PubMed1997

Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer.

PURPOSE: To determine whether a course of hyperfractionated radiation therapy concomitant with escalated radiosensitizing platinum compounds can be administered with acceptable morbidity and achieve a high rate of loco-regional control for Stage III and IV head and neck cancer and whether the patients can be tumor free at the primary site after initial therapy and cured by the additional chemoradiation without radical resection of the primary tumor. METHODS AND MATERIALS: Patients with Stage III/IV head and neck cancer were treated in this multicenter Phase II Study with 1.8 Gy fraction radiotherapy for 2 weeks, with escalation to 1.2 Gy b.i.d. hyperfractionation to 46.8 Gy. Concomitant continuous infusion cisplantinum (CDDP) 20 mg per meter square on day 1 to 4 and 22 to 25 was given. Reassessment by biopsy of primary and nodes was done. Patients with a complete response continued with hyperfractionated radiotherapy to 75.6 Gy with simultaneous carboplatinum (Carbo), 25 mg per meter square b.i.d. for 12 consecutive treatment days. Patients with residual disease at 46.8 Gy required curative surgery. Seventy-four patients were treated at the three institutions; 20 were Stage III and 54 were Stage IV. All patients had daily mouth care, nutritional, and psychosocial support. RESULTS: This regime was well tolerated. Eighty-five percent of toxicities were Grade 1 or 2 and there was only one Grade 4 hematologic toxicity. Late toxicities included xerostomia in 25 patients, dysphasia in 18, and mild speech impediment in 11. Biopsies of primary site were done after the first course of treatment in 59 patients. Neck dissections were performed in 35 patients. Forty-four of 59 (75%) primary sites and 16 of 35 (46%) lymph nodes had pathologically complete response (CR). Of the 74 patients, only 12 required surgical resection of the primary site. Thirty-five of the 50 node positive patients had neck dissections, 16 of these were CRs at surgery. At 4 years (median follow-up of 26 months), disease-specific survival is 63%. The actuarial survival for all patients is 51%. Patients with pathological CR after initial treatment have disease specific survival of 73% at 4 years vs. 48% of patients with partial response (PR) only. CONCLUSION: This study, developed on the basis of radiobiological and cell kinetic precepts, produced results that compare favorably with other reports of management of patients with advanced head and neck cancer. In comparison with our previous study, these results are comparable, not impressively better. The associated morbidity was somewhat worse.

Adult↗

PubMed2005

HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma.

BACKGROUND: The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS: The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a >/= 50% regression in clinical tumor size prior to surgery. RESULTS: In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu-negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2-13.0) in favor of docetaxel. Women who had HER-2/neu-negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu-positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS: HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu-negative tumors to match that observed in women who have HER-2/neu-positive tumors treated with AC alone.

Adult↗