Interrupted versus Continuous Chemotherapy in Patients with Metastatic Breast Cancer

Hb, Muss; Ld, Case; Richards, Frederick; Dr, White; Mr, Cooper; Jm, Cruz; Bl, Powell; Cl, Spurr; Rl, Capizzi

doi:10.1056/nejm199111073251904

Cited by 182 publications

(61 citation statements)

References 26 publications

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“…Whether intermittent chemotherapy offers any true advantage over continuous chemotherapy administered until progression with respect to longevity, morbidity, costs and quality of life in patients with advanced colorectal cancer can only be determined in a randomized controlled study. Median survival times reported in clinical trials using intermittent or continuous 5-FU/LV seem to be almost identical (Kohne-W6mpert et al, 1992), a finding that has already been confirmed in randomized trials of continuous vs discontinuous chemotherapy in advanced breast cancer (Coates et al, 1987;Muss et al, 1991). According to a shorter duration of cytotoxic drug administration/treatment-free interval between induction and reinduction, discontinuous chemotherapy is likely to offer an advantage in terms of cumulative toxicity, frequency and inconvenience of hospital visits, costs of treatment and quality of life.…”

Section: Discussionmentioning

confidence: 83%

Reinduction therapy with the same cytostatic regimen in patients with advanced colorectal cancer

Hejna

Kornek²,

Raderer³

et al. 1998

Br J Cancer

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Summary The aim of the study was to investigate the therapeutic value of reinduction therapy with the same cytostatic treatment that had been used for induction treatment in patients with metastatic colorectal cancer. A total of 71 patients, all of whom had responded or achieved stable disease lasting >12 weeks after six monthly courses of first-line treatment with 5-fluorouracil + racemic leucovorin (5-FU/LV; n = 35) or 5-FU plus the I-isomer of LV (LLV; n = 34) were entered in this study. At the time of relapse, the same treatment was used for initial therapy: racemic LV or LLV was administered at 100 mg m-2 day-' by i.v. bolus injection, immediately followed by 5-FU 400 mg m-2 day-1 given as a 2-h infusion. Chemotherapeutic drugs were given on 5 consecutive days at 4-week intervals x 6 or until there was evidence of tumour progression. Among 49 evaluable patients, reinduction therapy that was initiated after a median treatment-free interval of 5.4 months (range 3-14.5) resulted in nine partial response (PR) (18%) and 26 stable disease (SD) (53%), yielding an overall tumour control rate of 69% (95% confidence interval, 54.6-81.7%). The median time to treatment failure from reinduction was 6.4 months, and the median survival duration from reinduction was 8.9 months (20.1 months as judged from the beginning of induction therapy). The toxicity associated with retreatment was generally mild to moderate; compared with initial treatment, there was no significant difference in terms of the overall rate (P = 0.33) or severity (P = 0.19) of adverse reactions. Our data suggest that in patients with advanced colorectal cancer an interrupted treatment strategy, i.e. retreatment with the same regimen in case of relapse .3 months after discontinuation of 6 months of successful treatment with 5-FU/LV or 5-FU/LLV is an acceptable therapeutic concept.Keywords: advanced colorectal cancer; chemotherapy; reinduction; 5-fluorouracil; leucovorin Advanced colorectal cancer remains a therapeutic challenge to clinicians involved in the management of this common malignant disease, which continues to be the second leading cause of cancer death in the Western world (Chu et al, 1994). Despite intensive efforts to improve the poor prognosis of patients with advanced colorectal cancer, therapeutic progress has been hampered by its apparent chemotherapeutic refractoriness. Although randomized trials have established with reasonable certainty that fluorouracil/leucovorin-based chemotherapy results in substantive therapeutic gain compared with best supportive care (The Nordic Gastrointestinal Tumour Adjuvant Therapy Group, 1992;Scheithauer et al, 1993) or treatment with 5-FU alone (Poon et al, 1989; Advanced Colorectal Cancer Meta-Analysis Project, 1992), there is considerable room for further improvement in terms of the response rates and tolerance of treatment. Until now, it has not been possible to define the optimal regimen of biochemical modulation of fluoropyrimidines (Doroshow, 1996), and there is also sparse information in terms of the...

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Section: Discussionmentioning

confidence: 83%

Reinduction therapy with the same cytostatic regimen in patients with advanced colorectal cancer

Hejna

Kornek²,

Raderer³

et al. 1998

Br J Cancer

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“…Intermittent chemotherapy was first evaluated in patients with breast and colorectal cancers without adversely impacting overall survival (OS). [10][11][12] Interestingly, not only has the lack of benefit of prolonged chemotherapy been questioned by Cara, 13 Tannock 14 and Norton, 15 continuous chemotherapy has also been shown to result in the development of chemotherapy resistance. 8,14,16 Patients with CRPC who previously had discontinued DTX treatment have recently been reported to be sensitive to DTX re-treatment.…”

Section: Introductionmentioning

confidence: 99%

Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer: a single-arm prospective study using a historical control for comparison

Zhang²,

Tao-tao³

et al. 2013

Asian J Androl

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Whether continuous docetaxel (DTX) chemotherapy offers an advantage over intermittent therapy for castration-resistant prostate cancer (CRPC) is unknown. In this study, we evaluated the efficacy, toxicity and quality of life (QoL) of intermittent tri-weekly DTX with bicalutamide in CRPC. Forty-two patients (group A) with CRPC were enrolled. The patients received intravenous DTX (75 mg m 22 ) once tri-weekly with oral bicalutamide (50 mg) once daily. Patients had a DTX holiday when the prostate-specific antigen (PSA) level declined o50%. DTX was restarted in patients with a PSA increase o25%. Sixty patients (group B) who had matching characteristics and had continuously received DTX without bicalutamide for 10-12 cycles were also enrolled. There were no statistically significant differences in progression-free survival (8 months vs. 9 months, P50.866) or overall survival (19 months vs. 21 months, P50.753) between groups A and B; however, the proportions of patients in group A with all grades of neutropenia (33% vs. 58%, P50.013) and nausea/vomiting (11% vs. 29%, P50.024) were significantly less compared to group B. A significant improvement in the global health and fatigue scores was recorded for group A post-chemotherapy compared to pre-chemotherapy (P,0.05). The fatigue, nausea/ vomiting and appetite loss scores in group B were increased post-chemotherapy compared to pre-chemotherapy (P,0.05). In conclusion, intermittent tri-weekly DTX plus bicalutamide is well tolerated and has the potential to achieve comparable disease control with an improvement in QoL for patients with CRPC.

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“…Several trials over the past two decades have demonstrated consistent prolongation of progression-free survival (PFS); however, a survival benefit or quality of life (QoL) advantage has been infrequently documented. These studies have supported the use of more protracted chemotherapy regimens [2,[4][5][6][7]9]. Results of a meta-analysis demonstrated a modest, but statistically significant survival advantage for patients randomized to longer versus shorter treatments [11].…”

Section: Discussionmentioning

confidence: 95%

“…Although the role of maintenance therapy in MBC is still undefined, its goal is to prolong the primary therapy benefit and improve disease control, while maintaining an acceptable quality of life. To date, eight out of nine randomized trials of standard versus extended duration chemotherapy in MBC patients have consistently demonstrated a progression-free survival (PFS) advantage favoring extended duration therapies [2][3][4][5][6][7][8][9][10]. Unfortunately, these trials have failed to demonstrate a consistent benefit in overall survival (OS), and the additional cycles of chemotherapy were often associated with a significant increase in toxicity.…”

Section: Introductionmentioning

confidence: 99%

Maintenance treatment with Pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study

Alba

Ruíz‐Borrego

Margelı́

et al. 2010

Breast Cancer Res Treat

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This randomized multicenter phase III trial evaluated the role of maintenance therapy with pegylated liposomal doxorubicin (PLD) after induction chemotherapy in patients with metastatic breast cancer (MBC). Patients without disease progression following first-line induction chemotherapy consisting of three cycles of doxorubicin (75 mg/m 2 ) followed by three cycles of docetaxel (100 mg/m 2 ) both every 21 days, were randomized to PLD (40 mg/m 2 ) every 28 days for six cycles or to observation. Time to progression (TTP) was the primary endpoint. 288 patients were enrolled and received induction first-line chemotherapy. One hundred and fifty-five achieved response or stable disease and were randomized to maintenance PLD (n = 78) or observation (n = 77). With a median followup of 20 months from randomization (range 1-56), disease progression occurred in 94% of patients. 123Breast Cancer Res Treat (2010) 122:169-176 DOI 10.1007 two patients developed febrile neutropenia. This phase III trial demonstrated that maintenance chemotherapy with PLD is well tolerated and offers improved TTP in patients with MBC following first-line chemotherapy.

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Interrupted versus Continuous Chemotherapy in Patients with Metastatic Breast Cancer

Cited by 182 publications

References 26 publications

Reinduction therapy with the same cytostatic regimen in patients with advanced colorectal cancer

Reinduction therapy with the same cytostatic regimen in patients with advanced colorectal cancer

Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer: a single-arm prospective study using a historical control for comparison

Maintenance treatment with Pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study

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