Individually tailored toxicity-based 5-fluorouracil, epirubicin and cyclophosphamide (FEC) therapy of metastatic breast cancer

Figures & data

Table I.  Dose levels used for stepwise escalation or reduction

Dose levels	F mg/m^2	E mg/m^2	C mg/m^2	Mesna mg/m^2
Level -2	300	40	450	–
Level -1	600	60	600	–
Level 1*	600	75	900	–
Level 2	600	90	1200	240×3
Level 3	600	105	1500	300×3
Level 4	600	120	1800	360×3

*Starting level; F-5-fluorouracil; E-epirubicin; C-cyclophosphamide.

Table II.  Dose-modification schedule based on the recorded myelotoxicity after previous treatment cycle

	Day 8, 12 or 15 nadir counts		Day 22 count	Action
WBC/ PLT	≥1.0 and/ ≥ 75	and	≥3.0 and/ ≥ 100	Dose escalation 1 level next cycle
WBC/ PLT	<1.0 during < 5 days or/25–75	or	2.5–2.9 and/ ≥ 100	Repeat same level for next cycle
WBC/ PLT	<1.0 during ≥ 5 days or/ < 25	or	2.0–2.4 and/ ≥ 100	Reduce 1 level next cycle
WBC/ PLT	Febrile neutropenia/ Any	and	Any/75–99	Reduce 2 levels next cycle
WBC/ PLT	Any/Any	and	<2.0 or/ < 75	Delay next cycle by 1 week and reduce 1 level

WBC-white blood cells (×10⁹/L); PLT- platelets (×10⁹/L).

Table III.  Patient characteristics

Number of patients	26
Median age (range)	48 (32–59)
Hormonal receptor status
Positive	16 (62%)
Negative	5 (19%)
Unknown	5 (19%)
Adjuvant treatment
Chemotherapy (CMF)	12 (46%)
Hormonal therapy	5 (19%)
Median interval (months):
Primary diagnosis-relapse (range)	28 (0–80)
Primary diagnosis-metastases (range)	33 (0–143)
Primary diagnosis-study entry (range)	36 (0–144)
Dominating site of disease
Visceral	13 (50%)
Bone	7 (27%)
Soft tissue	6 (23%)
Number of organ involved
1	14 (54%)
2	7 (27%)
≥ 3	5 (19%)
Shortest follow-up time in years	9.4

CMF- cyclophosphamide, methotrexate and 5-fluorouracil

Figure 1.  Stacked column diagram showing the distribution of different dose levels during the study treatment of 9 cycles. The number of given dFEC cycles (n = 199) is presented at the Y-axis at each cycle (X-axis). The highest dose levels were delivered at cycle 4-6 and all patients but one (wrongly treated with level -1 at the first cycle), received the level 1 at the start.

Figure 2.  Kaplan-Meier diagram showing time to progression (TTP) and overall survival (OS) for patients in the present study (n = 26).

Table IV.  Treatment responses

Response	(n=26)	(95% CI)
CR + PR (OR)	21 (81%)	(66%–96%)
CR	6 (23%)	(7%–39%)
PR	15 (58%)	(39%–77%)
SD	4 (15%)	(2%–29%)
PD	1 (4%)	(0%–11%)

CR-complete response; PR-partial response; OR-overall response; SD-stable disease; PD-progressive disease.

Table V.  Worst grade reported toxicity per cycle (n = 199) and per patient (n = 26)

	All grades		Grade I		Grade II		Grade III		Grade IV
	/cycle	/patient	/cycle	/patient	/cycle	/patient	/cycle	/patient	/cycle	/patient
Nausea/vomiting	36%	88%	23%	35%	11%	35%	3%	12%	0
Mucositis	33%	81%	28%	54%	4%	23%	1%	4%	0
Muscle pain	12%	42%	9%	27%	2%	8%	1%	8%	0
Fever	22%	69%	11%	19%	12%	42%	1%	4%	0
Febrile leucopenia	5%	31%	0		0		5%	31%	0

Figure 3.  Diagram of the average quality of life (QoL) from start until cycle 9 (n = 22). Baseline values are normalized to 1.00 and a change of 0.1 units represents a 10% difference in QoL. The two global QoL endpoints of the EORTC QLQ-C30(+3) instrument are presented separately.