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Achim petry neue single Engl J Med ; On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens — cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone — in patients continue reading locally advanced cervical cancer.
Women with primary untreated achim petry neue single squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. All patients received external-beam radiotherapy according to achim petry neue single strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: Full Text of Background and Methods The analysis included women.
The median duration of follow-up was 35 months. The relative risks of progression of disease or death were 0.
The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0. Full Text of Results Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.
Full Text of Discussion Cervical cancer is the second most frequent cancer among women worldwide and the most frequent cancer among women in Africa, Asia, read more South America.
The ability of radiotherapy to cure locally advanced bekanntschaften afrikaner cancer is limited by the size of the tumor, because the doses required to treat achim petry neue single tumors exceed the limit of toxicity in normal tissue. Theoretically, chemotherapy and radiotherapy could have a synergistic effect; for example, the chemotherapy might increase the sensitivity of the tumor to radiation.
Moreover, radiotherapy could be used for local disease while chemotherapy is used for systemic disease. The Gynecologic Oncology Group has performed several prospective, randomized studies of the effect of concurrent chemotherapy and radiotherapy in women with locally advanced cervical cancer.
Radiotherapy combined achim petry neue single treatment with hydroxyurea has been compared in separate trials with radiotherapy alone, with radiotherapy and concomitant therapy with misonidazole, and with radiotherapy achim petry neue single concomitant treatment with cisplatin achim petry neue single fluorouracil and Whitney CW: As compared with radiotherapy alone, treatment with hydroxyurea and radiotherapy significantly increased the rate of complete response, progression-free survival, and overall survival.
At the time we were developing the protocol used in achim petry neue single current study, radiotherapy plus concomitant chemotherapy with hydroxyurea was the standard combined-therapy regimen for advanced cervical cancer, because an early analysis of the combination of radiation, cisplatin, and fluorouracil failed to show improved progression-free survival. Achim petry neue single, myelosuppression is a limiting toxic effect of treatment with hydroxyurea, whereas cisplatin is less myelosuppressive and can be given weekly during radiotherapy, with acceptable levels achim petry neue single toxicity.
In addition, the responses in phase 2 trials of this chemotherapy regimen with radiotherapy in patients with cervical cancer and in patients with head and neck cancer were favorable. The institutions that participated in the study are listed in the Appendix. Women with untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or achim petry neue single of the cervix of International Federation of Gynecology and Obstetrics stage IIB localized disease with parametrial involvementstage III extension of the tumor to the pelvic wallor stage IVB involvement of the bladder or rectal mucosa were enrolled in the study from April to April All cancers were confirmed histologically by the Gynecologic Oncology Group pathology committee.
Patients with disease outside the pelvis and those with metastasis to para-aortic lymph nodes or intraperitoneal disease were not eligible. Each partnersuche wissenschaft was required to undergo a complete physical examination, a pelvic examination click at this page anesthesia, chest radiography, and intravenous pyelography or abdominal computed tomography to determine the clinical stage of the cancer.
In addition, patients were required to have undergone a specific type of extraperitoneal para-aortic lymphadenectomy. Other eligibility criteria were as follows: Additional pretreatment evaluations included assessment of performance status and measurements of the please click for source tumor and serum electrolytes and magnesium.
All patients gave written informed consent according to institutional, state, and federal regulations. Radiotherapy was administered to the whole pelvic region in 24 fractions totaling Either one or two intracavitary achim petry neue single were inserted.
The total dose delivered to point A a reference location 2 cm lateral and 2 cm superior to the cervical os was Pelvic radiation was delivered by anteroposterior and posteroanterior parallel ports or a four-field box technique anteroposterior, posteroanterior, and two lateral fields with an x-ray energy of at least 4-MV photons. The pelvic field extended from the upper margin of L5 to the midportion of the obturator foramen or the lowest level of disease, with a 3-cm margin, and laterally 1.
Achim petry neue single the lateral fields, achim petry neue single anterior border was the anterior border of the pubic symphysis and the posterior border was the space between S2 Хотя dating whatsapp group вернулся S3. The fields could be modified to include areas of known tumor. If two intracavitary applications were used, the http://date.zum-schlosswirt-weimar.de/wo-einen-reichen-mann-kennenlernen.php was to be given within two weeks after the first implant.
If intracavitary brachytherapy could not be delivered, the tumor was treated with additional external-beam radiotherapy, for a total dose of Interstitial and high-dose brachytherapy were not allowed.
The duration of the radiotherapy was 10 weeks. Radiotherapy was withheld if a patient had a leukocyte count of less than per cubic millimeter, and delays of up to one week were also allowed in the event of radiation-related gastrointestinal or genitourinary please click for source. The length of delays in radiotherapy, in days, was calculated by subtracting the planned duration of radiotherapy the number of prescribed fractions plus 2 weekend days for every five fractions plus 10 days for each implant from the actual duration of radiotherapy.
The Radiological Physics Center in Houston reviewed all technical aspects of radiotherapy and verified the calibration of the instruments used.
The patients were randomly assigned to receive one achim petry neue single three chemotherapy regimens, which were given concomitantly with external-beam radiotherapy Table 1 Table 1 Chemotherapy Schedules and Dose Modifications.
Treatment with hydroxyurea or fluorouracil was discontinued if the leukocyte count dropped below per cubic millimeter or the platelet count dropped belowper cubic millimeter, and it was resumed once the counts rose above these levels. Treatment with cisplatin was discontinued if the leukocyte count dropped below per cubic millimeter or the platelet count dropped below 50, per cubic millimeter, and it was resumed once the counts rose above these levels.
Adverse effects that required modifications in the doses in subsequent cycles are shown in Table 1. The primary end points were survival and progression-free survival.
Progression was defined as a 50 percent increase in the product of the two largest diameters of the primary tumor or metastasis. Progression-free survival was calculated from the date of entry into the остановился singles bayern kostenlos прочитав to the date of the first physical or radiographic evidence of disease progression, death, or the last follow-up visit.
Survival was calculated from the date of entry into the study to the date of death or the last follow-up visit.
We calculated the target sample size of patients for each regimen on the basis of an ability to detect a 35 percent decrease in the rate of disease progression with the use of either radiotherapy combined with treatment with cisplatin or radiotherapy combined friedrichshafen singletreff treatment with cisplatin, fluorouracil, and hydroxyurea. The achim petry neue single called for final analysis when disease progression or death had occurred in patients receiving the control regimen radiotherapy combined with treatment with hydroxyurea.
This design provided the study with a statistical power of 80 percent with the use of the log-rank test at an alpha level of 0. Thus, because of the large difference in outcome among the treatment groups and the similarity between the rates of survival and progression-free survival within each of the treatment groups, this analysis is the final analysis of survival and progression-free survival.
See more was carried out by a block arrangement; the treatment assignments were stratified according to center and the three clinical stages of disease, with approximately equal numbers assigned to each treatment group. Life-table estimates were calculated according to the method of Kaplan and Meier, 23 and differences in progression-free survival were evaluated with use of achim petry neue single log-rank test according to the intention-to-treat principle.
Interim analyses were conducted in MayNovemberachim petry neue single November with the use of prespecified critical values The performance of these interim tests raised the type I error by only 0. Because of this negligible increase and to simplify the presentation, the P values were not adjusted for the results of the interim analyses. From April to Aprilpatients were enrolled: Forty-nine of these patients 9 percent were subsequently found to be ineligible for the following reasons: Thus, a total of patients were included in the analysis: There were no significant differences in the clinical characteristics among the three treatment groups Table 2 Table 2 Characteristics of the Patients.
The analyses reported here were performed click here December The relative risk of progression of disease or death was 0. Tick marks indicate patients with progression of disease. Numbers in parentheses are the achim petry neue single of patients at risk at four years. A multiple regression analysis of progression-free survival was achim petry neue single that included the prognostic variables identified by Stehman et al.
After adjustment for these five factors, the relative risks of disease progression for the group given radiotherapy combined with cisplatin therapy and the group given radiotherapy combined with treatment with cisplatin, fluorouracil, and hydroxyurea were extremely close relative risks, 0.
The rates of progression-free survival at 24 months were 67 percent in the group given radiotherapy combined with cisplatin therapy; 64 percent in the group given radiotherapy combined with treatment with achim petry neue single, fluorouracil, and hydroxyurea; and 47 percent in the group given radiotherapy achim petry neue single with hydroxyurea therapy. As of this writing, 75 percent of the patients have either died or have been followed for 30 months.
A source of patients have died 39 percent: After adjustment for achim petry neue single clinical stage of disease, the relative risk of death was 0. Tick marks indicate patients who died. A multivariate analysis of survival that was adjusted for the five prognostic factors identified by Stehman et al.
Patients in the group given radiotherapy combined with cisplatin therapy and the group given radiotherapy combined with treatment with cisplatin, fluorouracil, and hydroxyurea had less local progression 19 percent and 20 percent, respectively than those in the group given radiotherapy combined with hydroxyurea therapy 30 percent.
Patients in the two cisplatin-treated groups also had a lower frequency of lung metastases 3 percent and 4 percent, respectively than patients treated with hydroxyurea alone 10 percent. Eight patients did not receive any radiation therapy, and 41 8 percent received only external-beam treatment, achim petry neue single these 49 patients were evenly distributed among the three treatment groups.
The number of patients who received within 15 percent of the prescribed total dose to both point A 69 to 93 Gy and point B stage IIB, 47 to 63 Gy; stage III or IVA, 51 to 59 Gy was 90 percent in the group given radiotherapy combined with cisplatin therapy; 85 percent in the group given radiotherapy combined with treatment with cisplatin, fluorouracil, and hydroxyurea; and 84 percent in the group given radiotherapy combined with hydroxyurea therapy.
The median duration of treatment was 9. The median delay in administering radiotherapy was computed for the patients who received doses within 15 percent of the prescribed dose to both points A and B. The median delay was 8 days the 10th percentile was a time 2 days ahead of schedule, and the 90th percentile was a delay of 22 days in the group given radiotherapy combined with cisplatin therapy; 10 days 10th and 90th percentiles, 1 and 26 in the group given radiotherapy combined with treatment with cisplatin, fluorouracil, and hydroxyurea; and 8 days 10th and 90th percentiles, 1 day ahead of schedule and a delay of 23 days in the group achim petry neue single radiotherapy combined with hydroxyurea therapy.
There were no treatment-related deaths. The types and frequencies of adverse effects are shown in Table 4 Table 4 Adverse Effects. The highest combined frequency of grade 3 moderate and grade 4 severe adverse effects was associated with treatment with radiotherapy and the three-drug regimen; the frequency in the other two groups was similar.
Pelvic radiotherapy by itself fails to control the progression of cervical cancer in 35 to 90 percent of patients with locally advanced disease. Despite improvements in radiation equipment and techniques, in approximately two thirds of the cases, progression occurs within the area that was irradiated.
Since the para-aortic lymph nodes are often the first site of extrapelvic disease and involvement of these nodes was the most important prognostic factor in prior Gynecologic Oncology Group trials, only patients without involvement of the para-aortic lymph nodes were included in our study. We found higher rates of survival and progression-free survival among patients who were treated with radiotherapy and either cisplatin alone or cisplatin, fluorouracil, duden rechtschreibung kennenlernen hydroxyurea than among patients who were treated with radiotherapy and hydroxyurea alone.
Cisplatin is believed to augment the effects of radiation by inhibiting the repair of radiation-induced sublethal damage and achim petry neue single sensitizing hypoxic cells to radiation. In a study of 19 human cervical-cancer cell lines, Britten et al. The effects of chemotherapy should not interfere with the planned course of radiation, and one advantage of cisplatin is that it has limited adverse effects on bone marrow.
In our study, the rate of local recurrences was significantly lower with either cisplatin-based regimen than with the hydroxyurea regimen, whereas the rate of distant recurrences, specifically in the lungs, was only slightly less.
These results suggest that the principal effect of cisplatin is radiosensitization. The effect of radiotherapy with concomitant treatment with cisplatin alone has been studied in several achim petry neue single 2 trials.
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Geburtstag seine Songs in ihrer eigenen Interpretation und ihrem Stil neu zu produzieren. Das Album ging direkt von Null auf 1 und erreichte Gold.
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