Weekly systemic cisplatin plus locoregional hyperthermia: An effective treatment for patients with recurrent cervical carcinoma in a previously irradiated area

Figures & data

Table I.  Patient characteristics.

Patient characteristics
Age	Mean 46 yr (26–72)
WHO class
0	24
1	22
3	1
Histology
SCC	36
AC	11
Previous chemotherapy	8
Previous hyperthermia	12
Distant metastasis
absent	38
present	8
FIGO stage primary tumour
IB	20
IIA	5
IIB	9
IIIB	8
IVA	2
IVB	3
Time to recurrence	Mean 18 months (0–58)

SCC, squamous cell carcinoma; AC, adenocarcinoma.

Figure 1. Reasons to stop or delay treatment.

Table II.  Most severe toxicity observed per treatment series.

CTC-grade (%)	1	2	3	4
Anaemia	38	47	9	–
Trombopenia	28	19	15	–
Leucopenia	9	19	21	15
Neutropenia	9	14	14	21
Nephropathy	51	15	–	–
Constipation	13	15	3	–
Diarrhea	13	4	–	2
Neuropathy	21	2	–	–
Hearing	7	23	–	–
Fatigue	36	24	3	–
Nausea	36	34	2	4

Table III.  Responses inside and outside the heated area.

patient	Location of distant metastasis	Infield response	Outside response
1	para-aortal lymph nodes*	PR	SD
2	para-aortal lymph nodes*	PR	Unknown
3	bone, liver spleen	SD	PD
4	lung	PR	PR
5	liver	PR	SD
6	mediastinal lymph nodes	PD	PD
7	mediastinal lymph nodes	PR	SD
8	lung	SD	PD

*para-aortal lymph nodes are usually located at the rim of the hyperthermia applicator.

PR, partial response; SD, stable disease; PD, progressive disease.

Figure 2. Progression-free and overall survival.

Table IV.  Reports in literature on response rate for irradiated recurrent cervical carcinomas (reponses/no. evaluable)*.

Author	Cisplatin	Platinum-based regimen	Cisplatin and hyperthermia
Thigpen et al. [20]	7/20
Potter et al. [21]	7/32
Daly et al. [22]	7/14
De Murua et al. [23]		2/13
Lele et al. [24]		1/24
Ramm et al. [25]		3/20
Brader et al. [26]		3/57
Papadimitriou et al. [4]		3/11
Piver et al. [5]		3/10
Rose et al. [27]		5/21
Burnett et al. [28]		3/10
Fiorica et al. [29]		4/14
Gebbia et al. [30]		3/11
Matulonis et al. [7]		1/12
Rietbroek et al. [13]			12/23
Current study			26/47
Overall:	14/66 (31%)	31/203 (15%)	38/70 (54%)

*Only studies with ≥ 10 patients with previously irradiated recurrent cervical cancer were included.

Thigpen T, Shingleton H, Homesley H, Lagasse L, Blessing JA. Cisplatinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix. Cancer 1981; 48: 899–903

 PubMed Web of Science ®Google Scholar

Potter ME, Hatch KD, Potter MY, Shingleton H, Baker VV. Factors affecting the response of recurrent squamous cell carcinoma of the cervix to cisplatin. Cancer 1989; 63: 1283–1286

 PubMed Web of Science ®Google Scholar

Daly M, Cowie VJ, Davis JA, Habeshaw T, Junor EJ, Paul J, Pyper E, Reed M, Soukop M, Yosef H, et al. A short and intensive single-agent cisplatin regimen for recurrent carcinoma of the uterine cervix. Int J Gynaecol Cancer 1996; 6: 61–67

 Google Scholar

de Murua EO, George M, Pejovic MH, Dewailly J, Wolff JP. Combination cyclophosphamide, adriamycin, and cis-platinum in recurrent and metastatic cervical carcinoma. Gynecologic Oncol 1987; 26: 225–227

 PubMedGoogle Scholar

Lele SB, Piver MS. Weekly cisplatin induction chemotherapy in the treatment of recurrent cervical carcinoma. Gynecol Oncol 1989; 33: 6–8

 PubMedGoogle Scholar

Ramm K, et al. Bleomycin-ifosfamide-cis-platinum (BIP) in pelvic recurrence of previously irradiated cervical carcinoma: A second look. Gynecol Oncol 1992; 46: 203–207

 PubMedGoogle Scholar

Brader KR, Vergrote IB, Kaern J, Tropé CG. Chemotherapy for cervical carcinoma: Factors determining response and implications for clinical trial design. J Clin Oncol 1998; 16: 1879–1884

 PubMedGoogle Scholar

Papadimitriou CA, Sarris K, Moulopoulos LA, Fountzilas G, Anagnostopoulos A, Voulgaris Z, Gika D, Giannakoulis N, Diakomanolis E, Dimopoulos MA. Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix. J Clin Oncol 1999; 17: 761–766

 PubMed Web of Science ®Google Scholar

Piver MS, Ghamande SA, Eltabbakh GH, O’Neill-Coppola C. First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cancer of the cervix ã A phase II study. Gynecol Oncol 1999; 75: 334–337

 PubMed Web of Science ®Google Scholar

Rose PG, Blessing JA, Gershenson DM, McGhee R. Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study. J Clin Oncol 1999; 17: 2676–2680

 PubMed Web of Science ®Google Scholar

Burnett AF, Roman LD, Garcia AA, Muderspach LI, Brader KR, Morrow CP. A phase II study of gemcitabine and cisplatin in patients with advanced, persistent or recurrent squamous cell carcinoma of the cervix. Gynecol Oncol 2000; 76: 63–66

 PubMed Web of Science ®Google Scholar

Fiorica J, Holloway R, Ndubisi B, Orr J, Grendys E, Boothby R, DeCesare S, LaPolla J, Hoffman M, Patel J. Phase II trial of topotecan and cisplatin in persistent or recurrent squamous and non-squamous carcinomas of the cervix. Gynecol Oncol 2002; 85: 89–94

 PubMed Web of Science ®Google Scholar

Gebbia V, Caruso M, Testa A, Mauceri G, Borsellino N, Chiarenza M, Pizzardi N, Palmeri S. Vinorelbine and cisplatin for the treatment of recurrent and/or metastatic carcinoma of the uterine cervix. Oncology 2002; 63: 31–37

 PubMedGoogle Scholar

Matulonis UA, Campos S, Duska L, Krasner CN, Atkinson T, Penson RT, Seiden MV, Verrill C, Fuller AF, Goodman A. Phase I/II dose-finding study of combination cisplatin and gemcitabine in patients with recurrent cervix cancer. Gynecol Oncol 2006; 103: 160–164

 PubMed Web of Science ®Google Scholar

Rietbroek RC, Schilthuis MS, Bakker PJ, van Dijk JD, Postma AJ, Gonzalez GD, Bakker AJ, van der Velden J, Helmerhorst TJ, Veenhof CH. Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix. Cancer 1997; 79: 935–943

 PubMed Web of Science ®Google Scholar