Sequential Combination Of Chemotherapy Research Articles

Sequential Combination of Chemotherapy With Egfr-Tki As The First-Line Treatment for Unselected Patients With Advanced Non-Small Cell Lung Cancer: Systematic Review of Randomized Controlled Trials.

Sequential Combination of Chemotherapy With Egfr-Tki As The First-Line Treatment for Unselected Patients With Advanced Non-Small Cell Lung Cancer: Systematic Review of Randomized Controlled Trials.

Comments on “SEOM guidelines for endometrial cancer”

survival gain is outweighed by toxicity. Chemotherapy could be considered for women with a very high risk of metastatic disease who would otherwise have a long life expectancy. In the SEOR guideline and regarding the results of three pooled randomised clinical trials [3], NSGO-EC-9501/ EORTC-55991 and MaNGO ILIADE-III we can read ‘‘the combined modality treatment was associated with a statistically significant reduction in the risk of relapse and death’’. Patients were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy to analyse if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk EC. Pooling the data from both studies there was a highly significant difference in PFS favouring combined arm with HR 0.63 (95 % CI 0.41–0.99) P = 0.009. However, neither the NSGO/EORTC nor the MaNGO-trial showed significant differences in overall survival. The analysis of the pooled data approached statistical significance with HR 0.69 (95 % CI 0.46–1.03) P = 0.07).

Fludarabine Plus I-131 Tositumomab as Initial Treatment for Follicular Lymphoma: Half of Patients In Remission at Over 10 Years Median Followup.

AbstractAbstract 1785 Background:The sequential combination of chemotherapy and radioimmunotherapy has been shown to be effective front-line treatment for patients with follicular lymphoma (FL). We report ten-year followup results of a phase II trial of abbreviated fludarabine followed by tositumomab and I-131 tositumomab in patients with untreated follicular lymphoma. Methods:Patients with untreated follicular lymphoma received fludarabine 25 mg/m2/d for five days every five weeks for three cycles followed in six to eight weeks by tositumomab and I-131 tositumomab. Results:Thirty-eight patients were enrolled. One patient was withdrawn due to ineligible histology. The median age of eligible patients was 53 years, median time from diagnosis was 3.5 months, and 43% of patients had a high-risk FLIPI score. Two patients did not receive radioimmunotherapy; one patient had a myocardial infarction during fludarabine and was not evaluable, and one patient had persistent cytopenias following three cycles of fludarabine. All 35 patients that completed the regimen responded (ORR 100%). With a median follow-up of 128.5 months for all 37 eligible patients, the 10-year intent-to-treat overall survival is 69% and the progression-free survival is 51%. Seventeen patients have progressed (range 2–102 months). Sixteen patients remain in remission with no evidence of disease more than ten years from enrollment. Only four patients have relapsed beyond five years. Four patients have developed MDS (range 16–84 months), one of whom evolved to AML. Conclusions:Fludarabine followed by tositumomab and I-131 tositumomab is very effective at inducing long-lasting complete remissions in FL. The efficacy and long-term safety of sequential chemotherapy plus radioimmunotherapy should continue to be evaluated in the context of the range of therapeutic options for the initial treatment of follicular lymphoma. Disclosures:Furman:GSK: Speakers Bureau. Leonard:GSK: Consultancy.

Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer – Results from two randomised studies

Introduction Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled. Methods Patients ( n = 540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I–III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy. Results In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.41–0.99; P = 0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44–0.89; P = 0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46–1.03; P = 0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35–0.88; P = 0.01). Conclusion Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.

Primary localized stages I and II non-Hodgkin’s lymphoma of the nasopharynx: a retrospective 17-year single institutional experience

The aim of this retrospective study was to define the natural history, clinicopathological findings, prognostic factors, and treatment outcome of 43 patients with localized stages I and II primary non-Hodgkin's lymphoma (NHL) of the nasopharynx, followed up in a single institution over a 17-year period. Forty-three (13 women and 30 men) consecutive patients with localized stages I (N = 12) and II (N = 31) primary nasopharyngeal NHL were treated in our institution between 1990 and 2007. The pathologic reports were classified according to the International Working Formulation (N = 22) or Revised European-American Lymphoma classification (N = 21). The vast majority of patients (88%) were managed with a sequential combination of chemotherapy and radiation therapy. Chemotherapy mainly consisted of 4-8 (median 6) cycles of CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisolone). Involved-field radiation therapy with a median dose of 44 Gy was delivered to the primary site and entire cervical lymph nodes. The median age of the patients was 53 years (range, 6 to 86 years). The majority of the patients (70%) had high-grade histology. B-cell types represented 67% of the cases, among which diffuse large B cell was the most common histological subtype. After a median follow-up of 70 months, the 5-year disease-free survival and overall survival were 58.8% and 70.6%, respectively. In multivariate analysis, age less than or equal to 30 years (hazard ratio (HR) = 5.32, 95% confidence interval (CI) = 1.69-16.76), elevated serum lactate dehydrogenase level (HR = 3.69, 95% CI = 1.43-9.51), and modified International Prognostic Index with more than or equal to two risk factors (HR = 17.99, 95% CI = 2.32-139.30) retained statistical significance. Our limited data suggest that primary nasopharyngeal NHL tends to have aggressive histology and unfavorable clinical course with poor outcome, despite a considerably localized disease at the time of presentation and high frequency of complete initial response rates. Combined modality therapy should be considered for the majority of patients with primary localized nasopharyngeal NHL.

Durable remissions from fludarabine followed by the iodine I-131 tositumomab Bexxar therapeutic regimen for patients with previously untreated follicular non-Hodgkin's lymphoma (NHL)

6518 Background: The sequential combination of chemotherapy and radioimmunotherapy offers a novel strategy for the initial management of NHL. Tositumomab and iodine I 131 tositumomab (Bexxar) have been demonstrated to have substantial clinical activity in both untreated and relapsed/refractory low-grade NHL. Fludarabine synergizes in vitro with unlabeled and radiolabeled antibodies and can be employed as a “debulking” agent prior to radioimmunotherapy. Methods: Patients with previously untreated, advanced low-grade NHL were treated with IV fludarabine 25 mg/m2/day for 5 days, every 5 wks for 3 cycles followed in 6 to 8 wks by Bexxar therapy. Results: Between August 1998 and June 1999, 38 pts (51% follicular mixed, 49% follicular small cleaved) were enrolled and 97% had stage III/IV disease. Thirty-five subjects received both fludarabine and Bexxar therapy. Three patients came off study before or during fludarabine therapy (one due to cytopenias, 2 unrelated to toxicity or lymphoma progression). Response t...

Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-α after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen

Both chemotherapy and interleukin-2 and/or interferon-α produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m 2) and dacarbazine (DTIC, 750 mg/m 2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m 2 i.v. 3 days), cisplatin (DDP, 35 mg/m 2 i.v. 3 days), carmustine (BCNU, 150 mg/m 2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-α2 (rIFN-α). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13–26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5–14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-α, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-α. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-α were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-α had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.

Phase II randomized trial of radiotherapy alone vs the sequential use of chemotherapy and radiotherapy in stage III non-small cell lung cancer. Phase II trial of chemotherapy alone in stage IV non-small cell lung cancer

In order to clarify if the sequential combination of chemotherapy and radiotherapy offered any advantage over radiotherapy alone in stage III non-small cell lung cancer, 33 patients were randomized between radiotherapy alone or chemotherapy followed by radiotherapy, then chemotherapy again. Chemotherapy consisted of a combination of cisplatinum, VP-16 and adriamycin. Twenty-four patients with stage IV disease received the same chemotherapy regimen alone for six cycles. Median survival for stage III patients receiving radiotherapy alone was 5 months. For patients receiving the sequential combination of chemotherapy and radiotherapy median survival was 11 months (log-rank test, P = 0.025). Median survival for stage IV patient receiving chemotherapy alone was 15 months. It is concluded that the sequential combination of chemotherapy and radiotherapy is significantly superior to radiotherapy alone in patients with stage III non-small cell lung cancer.