Treatment for Cutaneous Melanoma Tumor Nodules

ABSTRACT & COMMENTARY

Synopsis: Ten patients were entered into a phase II clinical study to evaluate the anti-tumor effectiveness of electrochemotherapy with intratumoral cisplatin administration for melanoma tumor nodules. An objective response rate of 78% was seen four weeks after therapy in 82 tumor nodules treated with electrochemotherapy; and a 38% objective response rate was seen in 27 tumor nodules treated with cisplatin alone. Additional prospective randomized evaluation of this approach appears warranted.

Source: Sersa G, et al. Clin Cancer Res 2000;6:863-867.

Metastases to the skin and subcutaneous tissues are frequent sites of distant metastases for melanoma patients. Surgical excision remains an excellent means of palliation for patients with a limited number of skin and subcutaneous metastases, and patients can receive repeated excisions. However, alternative strategies are needed for patients with multiple or rapidly recurrent cutaneous and subcutaneous spread of melanoma. Local treatment options include intralesional injection of dinitrochlorobenzene (DNCB) or bacillus calmette-guérin (BCG) as well as carbon dioxide laser ablation.1 Regional radiotherapy can provide some palliation, and some of these patients receive limb perfusion or systemic therapy to palliate these nodules.1 However, additional local treatment strategies would be helpful for patients without concomitant spread to other organs or for patients refractory to systemic therapy.

The intratumoral administration of chemotherapy followed by delivery of electric pulses to tumor nodules is termed electrochemotherapy.2 The increased antitumor effectiveness of bleomycin and cisplatin combined with electric pulses has been suggested in prior experimental studies.3,4 The current study is designed to evaluate the antitumor effectiveness of electrochemotherapy using intratumoral cisplatin administration into cutaneous melanoma tumor nodules.

A total of 133 tumor nodules from 10 patients were evaluated in this study, and 82 tumor nodules received electrochemotherapy, 27 tumor nodules received intratumoral cisplatin alone, two tumor nodules received electric pulse therapy alone, and 22 tumor nodules were untreated. The median volume of the tumor nodules was similar in the electrochemotherapy treated group (median volume of 61 mm3; range 2-39270 mm3) and in the cisplatin treated group (median volume of 67 mm3; range 6-2094 mm3). Four weeks after therapy, objective responses were seen in 78% of the nodules receiving electrochemotherapy and in 38% of the nodules receiving cisplatin alone. The intratumoral injection of cisplatin was associated with some pain that lasted for a few minutes. The application of electric pulses to the tumor nodules was associated with contraction of muscles underneath the site of treatment, which resolved immediately after treatment. There were no significant systemic toxicities reported. Local toxicities included local erythema, slight local edema, and a superficial scab.

The administered dose of cisplatin ranged from 0.25 to 2 mg, depending on the size of the tumor nodule. The electric pulse treatment consisted of application of electric pulses with an electropulsator Jouran GHT 1287 with two parallel stainless steel electrodes having rounded tips and an inner distance between them of 7 mm. Nodules greater than 7 mm received several runs of electric pulses to achieve coverage of the entire tumor area. Treatment was administered on an outpatient basis. There was a four-week interval between repeated treatment sessions.

COMMENT BY MARK R. ALBERTINI, MD

While surgery remains an acceptable treatment for patients with limited cutaneous and subcutaneous metastases from melanoma, additional treatment options would be helpful for patients with multiple recurrent disease. Additional effective options to treat these metastatic nodules, especially in heavily pretreated patients, could provide reasonable palliation for these patients. Thus, clinical evaluation of electrochemotherapy as a treatment strategy for metastatic melanoma tumor nodules is clinically relevant.

Sersa and associates provide encouraging phase II results for control of metastatic melanoma tumor nodules. However, several points need to be considered. Important questions regarding dose and optimization of electric field distribution require further investigation. It remains unclear as to the effectiveness of this treatment for large tumor nodules. Thus, Sersa et al’s conclusion that "our results clearly demonstrate that electrochemotherapy with cisplatin is a highly effective approach for treatment of cutaneous malignant melanoma nodules" remains quite premature. However, sufficient data are provided to support a prospective randomized study evaluating electrochemotherapy with intratumoral cisplatin administration vs. intratumoral cisplatin administration alone for refractory melanoma patients with metastatic subcutaneous tumor nodules.

References

1. Meyers M, Balch C. In: Balch, Houghton, Sober, Soong, eds. Diagnosis and Treatment of Metastatic Melanoma in Cutaneous Melanoma. 3rd ed. 1998:325-372.

2. Mir LM, et al. Bioelectrochem Bioenerg 1995;38:203-207.

3. Sersa G, et al. Cancer Res 1995;55:3450-3455.

4. Mir LM, et al. Eur J Cancer 1991;27:68-72.

Which of the following statements about electrochemotherapy with cisplatin is true?

a. It is a new systemic treatment approach for patients with melanoma.

b. It uses electric pulses to enhance local effectiveness of chemotherapy.

c. It has established effectiveness for large tumor nodules.

d. It was established to treat tumor nodules located deep in the body.