Dose Intensity Of Adjuvant Chemotherapy Research Articles

The outcome of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 for resectable pancreatic ductal adenocarcinoma.

This study was performed to evaluate the efficacy of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 (S1-NACRT) for resectable pancreatic ductal adenocarcinoma. The medical records of 132 patients who received S1-NACRT for resectable pancreatic ductal adenocarcinoma from 2010 to 2019 were reviewed. The S1-NACRT regimen consisted of S1 at a dose of 80-120 mg/body/day together with 1.8Gy of radiation in 28 fractions. The patients were re-evaluated 4 weeks after S1-NACRT completion, and a pancreatectomy was then considered. Adverse events of S1-NACRT ≥grade 3 occurred in 22.7% of the patients, and 1.5% discontinued therapy. Of the 112 patients who underwent a pancreatectomy, 109 underwent R0 resection. Adjuvant chemotherapy with relative dose intensity ≥50% was administered to 74.1% of the patients who underwent resection. The median overall survival of all patients was 47 months, and the median overall survival and recurrence-free survival of patients who underwent resection was 71 and 32 months, respectively. According to the multivariate analyses of prognostic factors for overall survival in patients who underwent resection, negative margin status (hazard ratio: 0.182; P=0.006) and relative dose intensity of adjuvant chemotherapy ≥50% (hazard ratio 0.294; P < 0.001) were independent prognostic factors of overall survival. A multidisciplinary approach incorporating S1-NACRT for resectable pancreatic ductal adenocarcinoma demonstrated acceptable tolerability and good local control and resulted in comparable survival benefits.

Therapeutic efficacy of dose-reduced adjuvant chemotherapy with S-1 in patients with pancreatic cancer: a retrospective study

BackgroundS-1 adjuvant chemotherapy is the standard treatment in Asia for resectable pancreatic ductal adenocarcinoma. The relative dose intensity of adjuvant chemotherapy influences survival in pancreatic cancer but does not precisely reflect treatment schedule modifications. We investigated the effects of total dose intensity of S-1 adjuvant chemotherapy on the survival of patients with pancreatic cancer and the permissible dose reduction.MethodsPatients who underwent surgical resection during 2011–2019 for pancreatic cancer were selected. We determined the total dose intensity cut-off value that predicted tumor recurrence within 2 years postoperatively using receiver operating characteristic curves and compared the outcomes between the high and low total dose intensity groups.ResultsPatients with total dose intensity ≥ 62.5% (n = 53) showed significantly better overall survival than those with total dose intensity < 62.5% (n = 16) (median survival time: 53.3 vs. 20.2 months, P < 0.001). The median survival of patients without adjuvant chemotherapy (total dose intensity = 0, n = 28) was 24.8 months. Univariate analysis identified lymphatic involvement (P = 0.035), lymph node metastasis (P = 0.034), and total dose intensity (P < 0.001) as factors affecting survival. On multivariate analysis, total dose intensity (P < 0.001) was an independent predictor of worse survival.ConclusionsMaintaining a total dose intensity of at least 60% in S-1 adjuvant chemotherapy seems important to achieve a long postoperative survival in patients with pancreatic cancer.

Prognostic Impact of Relative Dose Intensity of Adjuvant Chemotherapy With S-1 on Pancreatic Ductal Adenocarcinoma.

Although adjuvant chemotherapy (AC) with S-1 is currently the standard treatment for pancreatic ductal adenocarcinoma (PDAC) in Japan, the associations between its relative dose intensity (RDI) and survival outcomes remain unclear. We reviewed 310 patients with PDAC who had undergone pancreatectomy from January 2014 to June 2020 at three institutions. Of these, patients who had received adjuvant S-1 monotherapy were analyzed. Patients who had died or developed recurrences within 6 months, or received neoadjuvant chemotherapy, were excluded from the analyses. Possible predictors of overall survival (OS), including RDI, were analyzed using Cox regression. The cutoff value for RDI was determined by receiver operating characteristic analysis. Ninety-four patients with a median age of 69 years (range=39-84 years) were analyzed. In the high-RDI group (RDI≥72.3%, n=74), the OS rates were 98.5% and 80.8% at 1 and 3 years, respectively, whereas in the low-RDI group (RDI <72.3%, n=20) they were 88.9% and 51.6%, respectively (p=0.001). By multivariate analysis, lymph node metastasis [hazard ratio (HR)=3.06; p=0.020], low RDI (HR=2.95; p=0.020), and time interval from surgery to initiation of AC > 51 days (HR=2.50; p=0.046) were independently associated with inferior OS. The combination of the latter two factors clearly stratified both OS and recurrence-free survival (p<0.001 and p=0.017, respectively). Early initiation and maintenance of RDI of S-1 monotherapy after pancreatectomy may improve the OS of PDAC patients.

Interpretation the Results of Adjuvant Chemotherapy in Curatively Resected Pancreatic Cancer

Abstract ESPAC-1 has established the role of adjuvant systemic chemotherapy in patients with pancreatic cancer after curative-intent resection. Recent observation-controlled studies further demonstrated that 6 months of gemcitabine monotherapy could double the recurrence-free survival, from 5.0-6.7 to 11.4-13.4 months, and reduced risk of death by 23-24% as compared to observation alone. Of interesting to note, the recurrence-free survival of patients receiving gemcitabine monotherapy decreased from 13.4-14.3 months in the CONKO-001 and ESPAC-3 and -4 studies to 11.3-12.8 months in the more recent launched CONKO-005 and PRODIGY 24/CCTG PA.6 studies. However, the median overall survival of those patients improved from 22.8 months in the 1998 launched CONKO-001 study to 26.5 months in the 2008 launched CONKO-005 study and 34.8 months in the 2012 launched PRODIGY 24/CCTG PA.6 study. The difference in median overall survival and median recurrence-free survival increased from 9.4 to 22.0 months during the 15-year period of time. Actually, several factors have been considered affect the median RFS and/or OS of patients with pancreatic cancer after the R0/R1 resection, such as the emergence of more effective primary chemotherapy for patients with recurrent or metastatic diseases, FOLFIRINOX and nab-paclitaxel plus gemcitabine, after 2010 and 2013, the applications of regular surveillance for early recurrence detection, the inclusion of patients with high CA 19.9 level and/or the proportion of patients with R0/R1 resection as well as the use of different definition of R0 resection, and dose intensity of adjuvant chemotherapy, etc. All of which will be discussed in the meeting.

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

SummaryBackgroundIncreasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy.MethodsTo clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs).FindingsIndividual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics.InterpretationIncreasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.FundingCancer Research UK, Medical Research Council.

Maintaining Dose Intensity of Adjuvant Chemotherapy in Older Patients With Breast Cancer

IntroductionMaintaining the relative dose intensity (RDI) of adjuvant chemotherapy at ≥ 85% has been associated with improved treatment outcomes in early-stage breast cancer (ESBC). Increasing evidence has suggested that patients aged ≥ 65 years can maintain the optimal RDI for standard chemotherapy regimens. The present study investigated the RDI of newer adjuvant chemotherapy regimens in this demographic. Patients and MethodsWe retrospectively analyzed the data from 281 patients aged ≥ 65 years with a diagnosis of ESBC who had received adjuvant chemotherapy across 3 sites in Queensland, Australia from 2010 to 2015. The primary endpoint was the proportion of patients who had received an RDI of ≥ 85%. ResultsThe median age at diagnosis was 68 years (range, 65-85 years), with 36.3% aged > 70 years. The patient characteristics included tumor stage T3 or T4 in 17% and node-positive disease in 60%. The common chemotherapy regimens included docetaxel/cyclophosphamide (23%), 5-fluorouracil/epirubicin/cyclophosphamide plus docetaxel or paclitaxel (17%); Adriamycin/cyclophosphamide/weekly paclitaxel (38%); and docetaxel/carboplatin/trastuzumab (11%). Primary (15%) and secondary (54%) granulocyte colony-stimulating factor (G-CSF) was used. An RDI of ≥ 85% was achieved in 63% of the patients. Significant associations were noted between a reduced RDI and age ≥ 70 years (P < .001), Charlson comorbidity index ≥ 1 (P = .043), initial dose reductions (P = .01), secondary G-CSF use (P = .45), hospital admission (P < .001), and febrile neutropenia (P = .007). Treatment-related toxicities were the most common reason for noncompletion, with high rates of hospital admissions (46%) and febrile neutropenia (22%). ConclusionOur findings suggest that patients aged ≥ 65 years with ESBC can maintain an optimal RDI with modern chemotherapy regimens. Appropriate geriatric assessment and the use of supportive measures such as G-CSF could better assist select groups to maintain an optimal dose intensity.

Clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for colorectal cancer.

867 Background: CAPOX as adjuvant chemotherapy is a standard care option for stage III and high risk stage II colorectal cancer(CRC). And then chemotherapy induced diarrhea (CID) is known as one of the dose-limiting toxicities for CAPOX. Although diverting ileostomy is useful for preventing serious complications of high risk anastomosis, it is well recognized that high ileostomy output is hard to manage. Furthermore, the effect of diverting ileostomy on CID of adjuvant chemotherapy is unclear. In this study, we addressed the clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for CRC. Methods: Patients who diagnosed with stage III colon cancer and stage II or III rectal cancer after curative surgery and received CAPOX as adjuvant chemotherapy during 2011- 2014 were reviewed retrospectively. We investigated the relationship between diverting ileostomy and dose intensity, toxicities and disease-free survival (DFS). Results: 112 patients (median age 60 years, 52% male, 69% colon cancer, 63% stage III, median follow-up 47 months) were enrolled in this study. Of 112 patients, 100 patients were received chemotherapy without ileostomy (non-ileostomy group: NIG) and 12 patients were received chemotherapy with ileostomy (ileostomy group: IG). 112 Patients received 870 chemotherapy cycles. All treatment related grade 3/4 adverse events were documented in 39% of patients in NIG and 33% of patients in IG (P = 0.77). Grade 3/4 of CID occurred in 8% of patients in NIG and 8% of patients in IG (P = 1). Grade 3/4 of neutropenia were recognized in 21% of patients in NIG and 17% of patients in IG (P = 1). Average relative dose intensity (RDI) in NIG were 75.7% and 85.8% for capecitabine and oxaliplatin, respectively. Average RDI of capecitabine and oxaliplatin in IG were 76.1% and 82.7%, respectively. Significant difference of RDI of capecitabine and oxaliplatin were not shown in comparison between NIG and IG (P = 0.93, P = 0.63). The 3-year DFS rate was 85.0% in NIG and 75.0% in IG. The HR for DFS for NIG compared to IG was 1.709 (95% CI, 0.49 to 5.95; P = 0.40). Conclusions: The presence of diverting ileostomy does not affect RDI of CAPOX as adjuvant chemotherapy.

The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma-including the analysis of clinicopathological factors influencing relative dose intensity.

Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated.A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed.Patients with RDIs ≥80% (n = 79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n = 55) (median survival time (MST): 45.6 months, 26.0 months, P < 0.001). Patients with no AC (n = 34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P = 0.79) or in those with <80% (P = 0.73). Patients in the S-1 monotherapy group (n = 49) showed significantly better OS than patients in the gemcitabine monotherapy group (n = 51) (MST: 95.0 months, 26.0 months, respectively; P = 0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P = 0.01), intraoperative blood transfusion (P = 0.005), lymph node metastasis (P = 0.03), and postoperative WBC count (P = 0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P = 0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P = 0.04) as independent predictors of poor RDI.Efforts to maintain RDI had a greater impact on survival than the struggle to start AC early after surgery. Intra-plus postoperative blood transfusion and a high postoperative PLR could be predictive markers of reduced RDI in AC of PDAC patients. Avoidance of perioperative blood transfusions where possible and nutritional support during the perioperative period could maintain adequate RDI and may lead to improved long-term outcome.

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Abstract P3-12-12: Body mass index does not influence febrile neutropenia and delivered dose intensity in adjuvant chemotherapy for breast cancer

Abstract Background Obese patients are often not fully dosed when receiving adjuvant chemotherapy for breast cancer, which might influence the inferior outcomes seen in this patient population. Current guidelines recommend full, weight-based dosing of chemoherapy for obese patients. The aim of the present study was to assess toxicity and deliverable dose intensity in patients treated with adjuvant chemotherapy for breast cancer. Patients and Methods We conducted a single-center retrospective case review on patients treated with adjuvant chemotherapy for early breast cancer at our institution from 2009 to 2012. Data were extracted from electronic patient records and side effect were graded according to CTC AE 3.0 in the source data. Statistics: Chi-Square, Fisher's exact test, MANOVA and repeated measures ANOVA. Software: SPSS 18. The study received approval from the local ethics comitee. Results We included 187 patients (185 female, 2 male) who received a total of 924 courses of chemotherapy with full eight-based dosing with either 6 courses of FEC-T (n = ,%) or TC (n = ,%). There were no differences accross BMI categories for age, gender, endocrine receptor expression, grading or her2-status. Obese patients had more unplanned admission (p = 0.008), infections (grade 3-4, p = 0.005, all grades, p = 0.025) and diarrhoe (all grades, p = 0.033) compared to normal-weight patients. This was not the case for overweight patients (p = 0.063, 0.322, 0.199, 0.107, 0.065). Obese and overweight patients had more constipation than normal-weight patients (all grades, p = 0.025 and 0.006, respectively). There were no signficant differences across weight categories for neutropenic fever, delivered dose intensity, dose reduction and premature discontinuation of therapy. Discussion Obese and overweight patients can be treated with full dose intensity and do not suffer from excessive serious complications compared to normal-weight patients. However, due to partly increased toxicity seen in obese patients, adequate supportive therapy is of particular importance. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-12.

Dose Intensity in Early-Stage Breast Cancer: A Community Practice Experience

Although nodal status, grade, size, and receptor status play roles in determining breast cancer prognosis, there is increasing evidence that maintaining dose intensity of adjuvant chemotherapy increases disease-free survival rate.

Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy

This retrospective study was undertaken to define risk factors for reductions in dose intensity of adjuvant chemotherapy in women with early stage breast cancer (ESBC). A nationwide survey of 190 community oncology practices was conducted between 1998 and 2002 with data collected retrospectively on 3,707 patients treated with adjuvant chemotherapy for ESBC. End points included reductions in dose intensity, delivered relative dose intensity (RDI) <85%, and the incidence of chemotherapy dose delays >/=7 days and dose reduction >/=15%. Demographic and clinical characteristics, incidence of febrile neutropenia (FN), and patterns of use of granulocyte colony-stimulating factor (G-CSF) were also assessed. Average RDI for all regimens was 88%, with 30% of patients receiving <85% of standard for their regimen. Seventeen percent of the reduction in average RDI was planned from the start of therapy, and 13% was unplanned. In univariate analysis, significant predictors of reduced RDI were: age >/=65 years (41%, P < 0.001), body surface area (BSA) >2 m(2) (37%, P < 0.001), negative lymph nodes (33%, P < 0.001), FN (36%, P = 0.013), and comorbidities (40%, P = 0.013), particularly renal disease (86%, P = 0.004). Dose reduction was less with prophylactic G-CSF (24%, P < 0.001). In multivariate analysis, significant independent predictors of reduced RDI included: advanced age, greater BSA, comorbidities, anthracycline-based regimens, a 28-day schedule and FN, while primary G-CSF prophylaxis was associated with a significant reduction in risk. A significant proportion of patients with potentially curable ESBC continue to experience planned and unplanned reductions in RDI.

Weekly 5-fluorouracil and leucovorin: achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection

BackgroundCurrent standard therapy following resection of high-risk colon cancer is intravenous bolus5-fluorouracil (5-FU) with leucovorin (LV), but there is no consensus on the optimum regimen of these drugs: practice ranges from the high toxicity Mayo Clinic schedule to the very low toxicity weekly QUASAR schedule. We present data for a weekly schedule that aims to provide moderately dose-intense treatment with low toxicity. Patients and methodsOne hundred and sixty-two patients were studied: 60% male; median age 65 years (36% over 70 years); 94% colorectal primary. Treatment was intravenous bolus (5 min) 5-FU 425 mg/m2 plus d,l-LV 45 mg flat rate once weekly, for a planned 24 weeks. Data for toxicity, dose-reductions, delays and stoppages were collected. ResultsOverall, 20% of patients experienced any grade ≥3 toxicity, most commonly diarrhoea (14% patients). Dose reductions were made in 35% of patients (although only 21% required 20% or more reduction); toxicity contributed to a decision to stop treatment before 24 weeks in 16% of patients. Median delivered dose intensity (DI) was 96% of planned (407 mg/m2/week) during treatment, and 91% of planned (385 mg/m2/week) over the full 24 week treatment plan. Female sex and age >70 years were significantly associated with higher rates of toxicity and dose adjustment, and lower delivered DI. ConclusionsWeekly treatment at these doses is convenient and well-tolerated for the large majority of patients, and achieves DI comparable with the 5 days a month QUASAR schedule and other more toxic standard regimens.

Dose Density in Adjuvant Chemotherapy for Breast Cancer

Background: Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. Methods: The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Results: Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN®) support are significantly greater than with conventional schedules (q21d). Conclusions: The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

Maintenance of Dose Intensity in Adjuvant Chemotherapy of Breast Cancer in Patients Treated Outside a Clinical Trial - Results of a Retrospective Study

Die Qualität der adjuvanten Chemotherapie beim Mammakarzinom ist von genereller Bedeutung seit die Aufrechterhaltung der absoluten Dosis und der totalen Dosisintensität der verabreichten Chemotherapie das Überleben der Patientinnen beeinflusst.

How important is dose intensity of adjuvant chemotherapy for early breast cancer? A comparison of physician perception with actual practice

How important is dose intensity of adjuvant chemotherapy for early breast cancer? A comparison of physician perception with actual practice

Increasing the dose intensity of adjuvant chemotherapy may improve the outcome of node-positive breast cancer patients

Increasing the dose intensity of adjuvant chemotherapy may improve the outcome of node-positive breast cancer patients

Racial disparity in the dose and dose intensity of breast cancer adjuvant chemotherapy.

The purpose of this study was to investigate the impact of race and obesity on dose and dose intensity of adjuvant chemotherapy. We abstracted data on patient/tumor characteristics, treatment course, physicians' intention to give a first cycle dose reduction, and reasons for dose reductions/delays from oncology records of 489 women treated from 1985 to 1997 in 10 treatment sites in two geographical regions. Administered doses and dose intensity were compared to standard regimens. Multivariate regression models determined the impact of race and body mass index (BMI) on dose proportion (actual:expected doses) and relative dose intensity (RDI) controlling for patient characteristics, comorbidity, chemotherapy regimen, site, and year of treatment. Logistic regressions explored race and BMI versus use of first cycle dose reductions. African-Americans received lower chemotherapy dose proportion and RDI than whites (0.80 vs. 0.85, p = 0.03 and 0.76 vs. 0.80, p = 0.01). In multivariate analyses, dose proportion was 0.09 lower (p = 0.002), and RDI was 0.10 (p < 0.001) lower in non-overweight African-Americans than whites. Obesity was associated with lower dose proportion (p < 0.01) and RDI (p < 0.03). Race and BMI were independently associated with first cycle dose reductions. Non-overweight African-Americans (p < 0.05) and overweight and obese African-American and white women (p < 0.001) were more likely to have first cycle dose reductions than non-overweight whites. We identified systematic differences in the administration of chemotherapy given to African-Americans and to overweight and obese women. These differences may contribute to documented disparities in outcome.

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy.

Audit of Cancer and Leukemia Group B Data

To the Editor: One of the cases reported in our paper “Dose and Dose Intensity of Adjuvant Chemotherapy for Stage II, Node-Positive Breast Carcinoma” (May 5 issue)1 came from St. Mary's Hospital in Montreal, an institution that is reported to have provided false information to the National Surgical Adjuvant Breast and Bowel Project. The Cancer and Leukemia Group B (CALGB) audited data from this hospital on April 13 and 14, 1994. As part of this audit, the primary data on the case reported in the CALGB 8541 trial were carefully reviewed and compared with the research record. Although we are . . .