Hyperthermia combined with intra-thoracic chemotherapy and radiotherapy for malignant pleural mesothelioma

Figures & data

Table I.  Patient and treatment characteristics.

No.	Age	Sex	PS before	Stage	Side	RT (Gy/fr)	Chemo	HT	Tmax
1	64	M	2	T3N1M0	R	2/1	Cb	2	44.2 t
2	54	F	1	T1N0M0	R	8/4	C	4	43.2 w
3	48	M	1	T2N2M0	L	10/5	Cb	5	42.3 w
4	77	F	1	T1N0M0	R	6/3	C	3	43.7 w
5	67	M	1	T1N0M0	L	10/5	C/Cb	5	40.1 s
6	76	F	1	T3N1M0	L	6/3	C	3	43.0 w
7	85	M	2	T3N2M0	L	3/3	Cb	3	42.8 i
8	51	M	2	T3N2M0	R	10/5	C	5	41.2 t
9	57	M	1	T3N0M0	R	6/3	C	3	42.7 w
10	71	M	0	T1N0M0	R	6/3	C	3	39.5 w
11	73	F	0	T2N0M0	R	4/2	C	2	35.4 s

RT: radiotherapy; Chemo: chemotherapeutic agents; HT: hyperthermia; M: male; F: female; C: CDDP; Cb: CBDCA; T_max: maximum temperature; t: tumour; w: chest wall; s: skin; i: intra-thoracic; fr: fraction. Median patient age was 65.7 years (range, 48–85 years) at initiation of treatment. Every patient underwent 2–5 courses of hyper-chemo-radiotherapy (median, 3.5 courses) without surgical treatment. T_max for the last two patients was not high, as thermocouples were placed near the skin surface and were thus susceptible to cold circulation water.

Figure 1. A patient receiving hyperthermia treatment. This patient is undergoing hyperthermia treatment. The catheter in the left chest is used for infusion of cisplatinum or carboplatinum.

Table II.  Treatment results.

No.	Age	Sex	Response	PS (after)	Discharge	Time/status
1	64	M	PR	1	yes	68.0 dead
2	54	F	PR	0	yes	27.4 dead
3	48	M	PR	0	yes	27.1 dead
4	77	F	SD	0	yes	38.1 alive
5	67	M	SD	0	yes	7.6 dead
6	76	F	SD	0	yes	6.5 dead
7	85	M	PD	1	yes	6.5 dead
8	51	M	PD	1	yes	4.1 dead
9	57	M	SD	0	yes	14.3 dead
10	71	M	SD	0	yes	17.1 alive
11	73	F	SD	0	yes	12.8 alive

All patients were discharged after hyper-chemo-radiotherapy due to pleural fluid control. PR was achieved in three of 11 patients (27.3%), SD in six patients (54.5%) and PD in two patients (18.2%). As of 11 June 2005, eight of 11 patients were dead due to primary disease and three patients were still alive. Survival time ranged from 4.1–68.0 months.

Figure 2. Overall survival. Overall survival for 11 patients with MPM. Median survival time (MST) was 27.1 months.

Table III.  Single-agent chemotherapy for MPM.

Reference	Patients	Drug	RR (%)
Lerner et al. [14]	51	Doxorubicin	14
Magri et al. [15]	21	Epirubicin	5
Bajorin et al. [16]	19	Mitomycin C	21
Zidar et al. [17]	35	Cisplatinum (21d)	14
Planting et al. [18]	14	Cisplatinum (7d)	36
Raghavan et al. [19]	31	Carboplatinum	16
Harvey et al. [20]	20	5-Fluorouracil	4
Solheim et al. [21]	60	Methotrexate	37
Van Meerbeeck et al. [22]	25	Paclitaxel	0
Steele et al. [23]	29	Vinorabine	24
Van Meerbeek et al. [24]	27	Gemcitabine	7
Anderson et al. [25]	26	Ifosfamide	4
Scagliotti et al. [26]	64	Pemetrexed	16

Most single agents have been tested for MPM. In general, monotherapy response rates are <20% and single-agent chemotherapy is thus not recommended for treatment of MPM.

Table IV.  Combination chemotherapy for MPM.

Drug	Patients	Response rate	MST (months)
ADM + CTX	36	11	8
ADM + CDDP	59	19	8.8
ADM + CDDP + MMC	24	21	11
CDDP + CPT-11	15	27	7
CDDP + MMC	35	26	7.7
CDDP + Vp-16	25	24	9.5
CDDP + GEM	21	48	10
CDDP + pemetrexed	456	41	12.1
CBPDA + pemetrexed	27	32	14.8

ADM: adriamycin; CTX: cyclophosphamide; MMC: mitomycin C; CPT-11: irinotecon;

Vp-16: etoposide; GEM: gemcitabine.

Combination chemotherapy regimens have been extensively evaluated in MPM. However, most response rates to these regimens are little higher than monotherapy and still <30% and MST remains in the range of 7–14.8 months.

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