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Biomedical subjects

David H Moore

Publications and source records attributed to David H Moore.

17 recordsLinked to original sources

Phase II clinical trial of capecitabine in the treatment of advanced, persistent or recurrent squamous cell carcinoma of the cervix with translational research: a gynecologic oncology group study.

PURPOSE: To evaluate the anti-tumor activity and adverse events of capecitabine in advanced, persistent or recurrent squamous cell carcinoma of the cervix, and to explore biomarkers with the potential to predict capecitabine response and toxicity. EXPERIMENTAL DESIGN: Eligible, consenting patients were treated with a starting dose of 2500 mg/m(2)/day or 1800 mg/m(2)/day (divided into two doses given every 12 h) for 14 days of each 21-day cycle. Prior chemotherapy was allowed only in the context of radiation "sensitization". Genotyping in the 5' and 3' ends of thymidylate synthase (TS) was performed in DNA from pretreatment blood. Relative gene expression of TS, dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) was quantified in RNA extracted from paraffin-embedded tumor. RESULTS: All patients had prior radiotherapy and 22 received a radiation sensitizer. A partial response was observed in 4 of 26 (15%) evaluable patients. An additional 35% of patients achieved stable disease while 42% experienced increasing disease. The most common serious non-hematological toxicities were gastrointestinal and dermatologic. Exploratory analyses suggested that: a germline polymorphism in the 3' or the 5' end of TS was not associated with TS gene expression, relative tumor expression of TS, DPD and TP were not correlated, and relative tumor expression of TP may predict severe anemia. CONCLUSIONS: Based on the modest response rate, this trial was closed without a second stage of accrual; single agent capecitabine was not selected for further study in advanced persistent or recurrent squamous cell carcinoma of the cervix previously treated with radiation or chemoradiation.

Adult↗

Association between cigarette smoking and prognosis in locally advanced cervical carcinoma treated with chemoradiation: a Gynecologic Oncology Group study.

OBJECTIVE: To determine if smoking, a known risk factor for a number of cancers including cervical cancer, is associated with poor prognosis in patients with locally advanced cervical carcinoma treated with chemoradiation. METHODS: Patients with primary, previously untreated, histologically confirmed stage II-B, III-B or IV-A cervical carcinoma participated in a Gynecologic Oncology Group (GOG) phase III study (GOG 165) and were randomly allocated to receive radiation plus either cisplatin or 5-fluorouracil. Smoking behavior was ascertained using an administered questionnaire and by quantifying urine cotinine concentration. Disease progression was defined as a >or=50% increase in the cross product of the existing tumor compared with previous assessments. Patients were followed until death. RESULTS: Of 328 enrolled patients, 12 were ineligible, one was inevaluable for reported smoking status and 40 others were inevaluable for cotinine-derived smoking status. Among evaluable patients, 133 (42%) were reported smokers and 111 (40%) were cotinine-derived smokers. The kappa for agreement between the groups was 0.872 (P<0.01). Compared with non-smokers, median survival was 15 months shorter for reported smokers and 20 months shorter for cotinine-derived smokers (P<0.01). After adjusting for covariates, a significant increase in the risk of death (but not disease progression) was observed for reported smokers (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.01-2.27; P=0.04) and cotinine-derived smokers (HR: 1.57; 95% CI: 1.03-2.38; P=0.04). CONCLUSIONS: Smoking predicts worse overall survival in women with locally advanced cervical carcinoma treated with chemoradiation.

Adenocarcinoma↗

Quality of life (QOL) outcomes from a randomized trial of cisplatin versus cisplatin plus paclitaxel in advanced cervical cancer: a Gynecologic Oncology Group study.

OBJECTIVE: Chemotherapy can profoundly affect patients' quality of life (QOL), yet few clinical trials in advanced cervical cancer have included QOL outcomes. Our purpose was to assess the impact of cisplatin (C) versus cisplatin plus paclitaxel (CP) on overall QOL and pain in cervical cancer patients. METHODS: QOL was assessed using FACT-Cx, consisting of the Functional Assessment of Cancer Therapy (FACT-G) plus a cervix cancer-specific subscale, the Brief Pain Inventory-Short Form (BPI-SF), and a neurotoxicity subscale. Time points were: baseline (prior to randomization) and prior to chemotherapy cycles 2, 3, and 4. RESULTS: Overall (FACT-G) scores did not differ significantly between arms at the fourth assessment (C = 70.3 (19.6); CP = 72.8 (17.4)). Scores were stable over time and considerably lower than the general population norms. The BPI-SF revealed a decline in pain scores in both arms from the first to fourth assessments. The CP arm produced a significantly higher response rate and progression-free survival (PFS) but not overall survival (OS). Greater myelosuppression was reported in the combination arm. The rate of QOL drop-out for any reason was higher for C (53%) compared to CP (38%) (P < 0.05). At the fourth time point, 60% of living patients in both arms completed a QOL assessment. CONCLUSION: There was no significant difference in overall QOL scores between treatment arms or serially. Combined with QOL results, the significant increase in response and PFS in the CP arm and the higher drop-out rate in the C arm suggest a better outcome for the combination regimen despite its increased myelosuppression.

Adult↗

Cervical cancer.

Worldwide, cervical cancer is the second most common malignancy in women and a major cause of morbidity and mortality. Until recently, the greatest strides in reducing cervical cancer mortality have occurred with the advent and implementation of screening programs. Many important advances have also taken place in the diagnosis and treatment of cervical cancer. This review article will highlight diagnostic and staging considerations with an emphasis on newer imaging modalities and how they might augment approved FIGO clinical staging. Management alternatives for patients with early-stage disease, locally advanced (stage IIB-IVA) disease, and metastatic cervical cancer will be discussed. Whenever possible, these discussions will unfold through an overview of pertinent clinical trials and current controversies.

Biopsy↗

Chemotherapy for recurrent cervical carcinoma.

PURPOSE OF REVIEW: If chemotherapy becomes the only treatment option for cervical cancer, the prognosis has traditionally been regarded as dismal. Data from several recent trials have demonstrated significant improvements in outcome with specific cisplatin-containing combinations. The purpose of this review is to highlight the evolution of phase III trials leading to current treatment standards. RECENT FINDINGS: Given the modest activity of single-agent cisplatin, devoid of any meaningful impact on survival, prospective studies focused on other drugs that might prove either more effective than, or could be used in combination with, cisplatin. Both paclitaxel and topotecan, in combination with cisplatin, yielded superior response rates and progression-free survival without diminishing patient-reported quality of life; however, only cisplatin plus topotecan also improved overall survival. Furthermore, patient-reported quality of life is not diminished despite the greater acute toxicity of combination regimens. SUMMARY: Despite these chemotherapeutic advances, median survival is still less than one year and most patients do not respond to treatment. It is important that investigators identify those patients who should participate in investigational trials of non-platinum-containing regimens. The next generation of clinical trials should explore emerging biological therapies.

Antineoplastic Combined Chemotherapy Protocols↗

Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study.

PURPOSE: Concurrent chemoradiotherapy is the standard of care for locally advanced cervix cancer; the optimal chemotherapy regimen is not yet defined. This trial was designed to compare the outcome of protracted venous infusion (PVI) fluorouracil (FU) with standard weekly cisplatin and concurrent radiation therapy (RT). PATIENTS AND METHODS: Patients with stage IIB, IIIB, and IVA cervical cancer with clinically negative aortic nodes were eligible. Pelvic RT dose was 45 Gy with a parametrial boost to involved sides of 5.4 to 9 Gy, and high- or low-dose rate intracavitary brachytherapy. Standard therapy was weekly cisplatin 40 mg/m2, and experimental therapy was PVI FU 225 mg/m2/d for 5 d/wk for six cycles during RT. RESULTS: The study was closed prematurely when a planned interim futility analysis indicated that PVI FU/RT had a higher treatment failure rate (35% higher) and would, most likely, not result in an improvement in progression-free survival compared with weekly cisplatin/RT. The PVI FU/RT arm continues to show a higher risk of treatment failure (relative risk [RR] unadjusted, 1.29) and a higher mortality rate (RR unadjusted, 1.37). There was no difference in pelvic treatment failure between regimens, but there was an increase in the failure rate at distant sites in the PVI FU arm. CONCLUSION: In this study, PVI FU does not show improved outcome over weekly cisplatin. Future research should explore combinations of FU with cisplatin, new radiosensitizers, and active drugs combined with RT to reduce the high rate of pelvic and distant treatment failure still seen in advanced cervix cancer.

Adult↗

Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study.

OBJECTIVE: A phase II study was conducted to evaluate the role of adjuvant intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy in patients with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC), after complete surgical staging. METHODS: Patients were required to have undergone complete surgical staging including maximal surgical resection. Residual < or =3 mm intraperitoneal disease, and pelvic and para-aortic lymph node dissection with negative nodes, were required. A dose of 15 mCi of intraperitoneal 32P was administered within 8 weeks of surgery. Vaginal brachytherapy was delivered using either high dose rate, total dose of 2100 cGy in 3 fractions (700 cGy per fraction prescribed to 0.5 cm depth from the vaginal surface) or low dose rate to 6500 cGy (prescribed to the vaginal surface) in 1-2 fractions. RESULTS: For the 21 evaluable patients, distribution by FIGO stage was as follows: Stages I-IIB (17), Stages III-IV (4). The median follow-up was 39.6 months (range: 5-63 months). No patients experienced grade 2-4 complications from their adjuvant therapy. Five patients suffered a recurrence: intraperitoneal [n = 2], distal vaginal [n = 2], and one at the surgical scar. Following the 2 distal vagina recurrences early in the trial, the entire length of the vagina was treated with intracavitary brachytherapy. No additional vaginal recurrences were observed. The two-year overall survival, cause-specific survival, and disease-free survival for the entire series were 89.2%, 89.2%, and 79.7%, respectively. CONCLUSIONS: Adjuvant therapy for UPSC and CCC with intraperitoneal 32P and vaginal brachytherapy after comprehensive surgical staging is feasible, well tolerated, and warrants further study on a larger scale.

Adult↗

Secondary surgical cytoreduction for advanced ovarian carcinoma.

BACKGROUND: We evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery. METHODS: Women were enrolled within six weeks after primary surgery. If, after three cycles of postoperative paclitaxel plus cisplatin, a patient had no evidence of progressive disease, she was randomly assigned to undergo secondary cytoreductive surgery followed by three more cycles of chemotherapy or three more cycles of chemotherapy alone. RESULTS: We enrolled 550 women. After completing three cycles of postoperative chemotherapy, 216 eligible patients were randomly assigned to receive secondary surgical cytoreduction followed by chemotherapy and 208 to receive chemotherapy alone. Surgery was declined by or medically contraindicated in 15 patients who were assigned to secondary surgery (7 percent). As of March 2003, 296 patients had died and 82 had progressive disease. The likelihood of progression-free survival in the group assigned to secondary surgery plus chemotherapy, as compared with the chemotherapy-alone group, was 1.07 (95 percent confidence interval, 0.87 to 1.31; P=0.54), and the relative risk of death was 0.99 (95 percent confidence interval, 0.79 to 1.24; P=0.92). CONCLUSIONS: For patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal, the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival.

Adult↗

Phase II study of cisplatin and vinorelbine in squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To evaluate the efficacy and toxicity of intravenous cisplatin and vinorelbine as combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between August 1997 and January 2001, 73 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Eligible patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. The initial doses administered were cisplatin 75 mg/m(2) every 4 weeks and vinorelbine 30 mg/m(2) weekly. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity and protocol guidelines. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria. RESULTS: Of 73 patients, 67 were eligible and assessable. The overall response rate was 30% (five complete and 15 partial responses). The overall median response duration was 5.5+ months. The major toxicity was neutropenia, with 16% grade 3 and 67% grade 4 reported. Gastrointestinal and neurotoxicity were infrequent and mild. CONCLUSION: The combination of cisplatin and vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population.

Adult↗

Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS: Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

Adult↗

An assessment of age and other factors influencing protocol versus alternative treatments for patients with epithelial ovarian cancer referred to member institutions: a Gynecologic Oncology Group study.

OBJECTIVE: To assess the frequency with which patients with epithelial ovarian cancer are enrolled in prospective Gynecologic Oncology Group (GOG) treatment studies and to assess whether enrollment is influenced by patient age or other factors. METHODS: The study was open to patients with primary, previously untreated epithelial ovarian cancer referred to member institutions. Eligible patients provided written informed consent to have demographic and medical records data submitted to the protocol database for analysis. Pathologic diagnosis was confirmed by central review. Demographic and clinical data, including coexisting medical conditions, tumor stage, grade, and histology, surgical procedures, planned postoperative therapy, and reason/s (if applicable) a patient was not treated per GOG protocol, were collected. RESULTS: Nine hundred and forty-eight patients were initially eligible. Subsequently, 137 (15%) patients were excluded based on pathology (low malignant potential tumors), as were 10 whose invasive disease was unstaged. Among 801 eligible patients, 36% were > or =65 years of age, 52% had papillary serous tumors, and 73% had stage III/IV disease. In patients aged <65 years, 67% were stage III/IV compared to 82% of patients > or =65 years of age. The mean age was 5.5 years greater for patients with stage III/IV versus stage I/II disease. Compared to their younger counterparts, older patients with stage III/IV disease were less likely to enter into a GOG treatment protocol. Most common reasons were patient ineligibility (33%), refusal (29%), and investigator decision (20%). CONCLUSION: Age appears to be an important factor influencing treatment selection among patients with stage III/IV ovarian cancer. In addition to reviewing eligibility criteria, practitioners' attitudes should be monitored to assure that elderly patients are not inappropriately denied participation in GOG clinical trials.

Age Factors↗

Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group.

PURPOSE: The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy. MATERIALS AND METHODS: The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing. RESULTS: Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed. CONCLUSION: Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.

Adult↗

Studies of apurinic/apyrimidinic endonuclease/ref-1 expression in epithelial ovarian cancer: correlations with tumor progression and platinum resistance.

PURPOSE: A crucial step in the DNA base excision repair pathway involves the cleavage of an apurinic/apyrimidinic site by an apurinic/apyrimidinic endonuclease (APE). The major APE in mammalian cells is APE/ref-1, a multifunctional enzyme that acts not only as a DNA repair enzyme but as a redox-modifying factor for a variety of transcription factors. The purpose of this study is to determine whether APE/ref-1 expression differs with ovarian cancer progression and metastasis and in platinum-resistant disease. EXPERIMENTAL DESIGN: Ovarian tissue sections were obtained from the Cooperative Human Tissue Network for studies of APE/ref-1 expression and the metastatic process and from our institutional Department of Pathology for studies of APE/ref-1 expression and platinum resistance. Tissue microsections from formalin-fixed, paraffin-embedded specimens of epithelial ovarian cancers were stained using a monoclonal antibody to APE/ref-1 followed by standard immunohistochemical techniques. Slides were then analyzed for the percentage of positively staining nuclei as well as staining intensity using a blinded coding system. RESULTS: All epithelial ovarian cancers expressed APE/ref-1. There were no significant differences in the percentage or intensity of nuclear staining in primary tumors from patients with early- versus advanced-stage disease or in primary tumors versus metastasis from patients with advanced disease. Both platinum-sensitive and platinum-refractory tumors demonstrated a range from minimal to high intensity staining nuclei with a median value of 2+ staining on a scale of 0-3+. The median value for the percentage of nuclei involved was 70% in the platinum-sensitive group and 90% in the platinum-refractory group (P = 0.118). CONCLUSIONS: APE/ref-1 expression is ubiquitous among epithelial ovarian cancers and is unaltered with the metastatic process. APE/ref-1 expression does not appear to differ between platinum-sensitive and platinum-refractory ovarian cancers and thus is not a useful biomarker for platinum resistance. Combined with evidence that APE/ref-1 expression and function may not be equivalent in all cell types and tissues, future work will investigate APE/ref-1 as a potential therapeutic target.

Antibodies, Monoclonal↗

A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: Docetaxel is an inhibitor of microtubule depolymerization and has demonstrated activity in paclitaxel-resistant breast cancer and gynecologic cancer. The Gynecologic Oncology Group (GOG) conducted a study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma to determine its activity, and nature and degree of toxicity, in this cohort of patients. METHODS: Patients with platinum- and paclitaxel-resistant ovarian or peritoneal carcinoma, defined as progression while on or within 6 months of therapy, were eligible if they had measurable disease and had not received more than one chemotherapy regimen. Docetaxel at a dose of 100 mg/m(2) was administered iv over 1 h every 21 days. A prophylactic regimen of oral dexamethasone 8 mg bid was begun 24 h before docetaxel administration and continued for 48 h thereafter. Hepatic function was strictly monitored. RESULTS: Sixty patients were entered and treated with a total of 256 courses, with all 60 evaluable for toxicity and 58 evaluable for response. Responses were observed in 22.4% of patients, with 5.2% achieving complete response and 17.2% achieving partial response (95% CI, 12.5-35.3%). The median duration of response was 2.5 months. The likelihood of observing a response did not appear to be related to the length of the prior paclitaxel-free interval or duration of prior paclitaxel infusions. The principal adverse effect of grade 4 neutropenia occurred in 75% of patients. There was one treatment-related death. Dose reductions were required in 36% of patients. CONCLUSIONS: Docetaxel is active in paclitaxel-resistant ovarian and peritoneal cancer but, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule.

Adult↗

Treatment of stage IB2 (bulky) cervical carcinoma.

Tumour size is an important prognostic factor in patients with stage IB cervical cancer. The patient with stage IB2 (bulky) cervical cancer represents a therapeutic challenge. Neither radical hysterectomy nor primary radiation therapy are sufficiently effective and are associated with significant treatment-related complications including ovarian failure and psychosexual deficits. A number of phase III studies have explored alternative management approaches in this patient population. It appears that extrafascial hysterectomy following radiation therapy does not improve overall survival relative to radiation therapy alone. Consistent with results seen in locally advanced cervical carcinoma, chemoradiation therapy is superior to radiation therapy alone as primary treatment for stage IB2 cervical cancer and as adjuvant therapy for surgically treated patients with high-risk factors for recurrence. Neoadjuvant chemotherapy has resulted in high clinical response rates and operability rates. There are two phase III trials suggesting an improvement in survival with neoadjuvant chemotherapy followed by radical hysterectomy versus either surgery (and selected postoperative radiation) or radiation therapy alone. These emerging treatments should be scrutinized in prospective controlled trials.

Adult↗

Neoadjuvant chemotherapy for cervical cancer.

None of the current surgical or radiation treatment strategies for cervical cancer satisfactorily leads to a high disease-free survival and a low risk for treatment-related complications in patients with bulky or locally-advanced disease. Neoadjuvant chemotherapy (NACT) prior to surgery or radiation therapy has been studied as a means to reduce tumour bulk and thereby rendering subsequent therapy more effective. Impressive clinical response rates to cisplatin-based NACT have been achieved with acceptable toxicity and survival. Of the patients treated, approximately 20% will achieve a complete clinical response and many of these patients will prove to have a complete pathological response. Although there are too few randomised controlled studies to determine the effectiveness of NACT approaches, relative to standard treatments.

Antineoplastic Agents↗

The role of radical hysterectomy and neoadjuvant chemotherapy in carcinoma of the cervix.

The patient presenting with a bulky stage IB2 cervical cancer is a therapeutic challenge. None of the current surgical or radiation treatment strategies satisfactorily leads to a high rate of disease-free survival and a low risk of treatment-related complications including ovarian failure and psychosexual deficits. Neoadjuvant chemotherapy may allow for reductions in tumor bulk, thereby rendering radiation therapy more effective or surgery more feasible. Impressive clinical response rates to cisplatin-based neoadjuvant chemotherapy have been achieved with acceptable toxicity. Approximately 20% of patients achieve a complete clinical response, and many also experience a complete pathologic response. There are still too few comparative studies and phase III trials to assess the effectiveness of neoadjuvant chemotherapy and radical surgery relative to standard treatments.

Antineoplastic Combined Chemotherapy Protocols↗