Effectiveness of cisplatin, adriamycin and cyclophosphamide combination chemotherapy

in the treatment of metastatic apocrine carcinoma: a case report and review of the literature

Abstract

We report a case of metastatic apocrine carcinoma arising from the peri-anal region. Partial response was achieved after a course of the combination chemotherapy with evidence of clinical, biochemical and radiological improvement. There are seldom reports available on the treatment of the primary or advanced disease, in particular the role of chemotherapy is not well defined.

Case report

A 49 year old man was presented in February 2000 with a subcutaneous nodule of 1cm in the peri-anal region. Wide excision of nodule was performed (5x1.5cm). The histology revealed poorly differentiated apocrine carcinoma with hyperchromic and pleomorphic nuclei and high mitotic activity (fig 1).The patient received no adjuvant treatment and the patient remained disease-free until June 2002 when he noticed right-sided and back pain. On examination, he had a 2cm right inguinal node and multiple left cervical lymph nodes. Core biopsy confirmed metastatic apocrine carcinoma. His liver function deranged reports showed alkaline phosphatase of 271 IU/L (normal range, 30-90 IU/L), alanine phosphatase of 74 IU/L (normal range, <58 IU/L) and serum carcino embryonic antigen (CEA) level 410 µg/L. Chest x-ray and skeletal survey were normal. Computed axial tomography of the abdomen showed multiple liver metastasis and L3 and lytic lesions in the T11 and L3 region. Extensive bony metastasis was confirmed with magnetic resonance imaging (MRI) of the pelvis.

The patient was treated with combination chemotherapy of cisplatin 50mg/kg, adriamycin 50mg/kg and cyclophosphamide500mg/kg every 3 weeks. After 2 cycles of chemotherapy, he had less pain and the right inguinal lymph node resolved with a decrease in the size and number of the left cervical lymph nodes. The serum CEA level decreased to 25.7 µg/L. Plain radiograph showed diminished lytic lesions. On serial ultrasounds, the metastatic liver nodules had also reduced in size and number. The chemotherapy was stopped after 5 cycles. As there was a clinical complication of reactivation of hepatitis B., Lamivudine was commenced and the patients liver function improved after 2 months treatment.

In summary, we achieved > 50% partial response after 5 courses of cisplatin, adriamycin and cyclophospamide. However in January 2003, we noted rising CEA levels worsening liver function. One month later the patient had increased pain in his back and legs and recurrent lymph nodes at previous sites. His alkaline phosphatase and alanine aminotransferase were 1006 IU /L, and 109 IU/L respectively. The serum CEA level increased to 1725µg/L. plain x-ray revealed extensive osteolytic lesions in pelvis and spine .Three cycles of taxol and carboplatin were given but the response was poor. He subsequently received palliative radiotherapy to the L1 to L5 region and the right hemi-pelvis and died in September 2003.

Discussion

Apocrine carcinoma of the skin is rare and affects males and females equally in all races. The most common sites are the axilla and scalp although other sites such as chest, eyelids, wrist, vulva, lips, pubic skin, finger tips, and cystic teratoma of the ovary have also been reported. Although, aetiology is uncertain the sunlight may play a role.

The biological behaviour of apocrine carcinoma is diverse but, in general, moderately and poorly-differentiated tumours behave more aggressively. Metastasis commonly involve the regional lymph nodes (100%)¹ . And, 48% of patients have distant metastasis such as bone, lung, skin, brain and kidney² .The prognostic factor include size, histological type and lymph node involvement. The 5-and 10-year survival rates for patients without lymph node involvement are 67% and 56% respectively³. The 5-year survival rate for metastatic disease is 29% with a 10-year survival rate of 9%. The primary treatment is surgical excision. Lymph node dissection is indicated for recurrent disease or for patients with moderately-or poorly-differentiated carcinoma³.

Post- operative treatment irradiation is believed to prevent recurrence or metastasis but some author have reported that the tumour is radio-resistant³. The role of chemotherapy is debatable and the responses in the past have generally been poor (Table. 1)^3-7. The reason that we used cisplatin, adriamycin, and cyclophosphamide in treating metastatic apocrine carcinoma is based on our experience of treatment of adenocarcinoma of unknown primary with cisplatin and doxorubicin based combination therapy. We have observed 63% objective and 26% complete response achieved in our study⁸.Patients treated with either cyclophosphamide or doxorubicin or both have a better median survival. Our centre has reported a 12.9% response rate in treating adenocarcinoma of unknown primary using cisplatin, adriamycin, and cyclophosphamide¹⁰.

Conclusion

The prognosis of metastatic apocrine carcinoma is grave but our experience of using cisplatin, adriamycin, and cyclophosphamide in treating metastatic disease is encouraging. Hence, we recommend this combination therapy since a good clinical, biochemical and radiological response was observed for our patient.

References

1.  Jacobson Yg  Rees Td granth  Fitchett vh:  Metastasizing
Sweat Gland Carcinoma: Arch surg. 78: 574-581, 1959.

2.  Qi Hz: Clinical  Manifestication and Treatment of Sweat Gland 
carcinoma  analysis of 22 cases : Chung hua chung liu tsa chih .10: 469,
1988.

3.  El Domeri a A  Brasfield Rd  Huvos ag  Stromg Ew: Sweat
Gland carcinoma  a clinicopathological study of 82 patients :Ann surg .
173: 270-274, 1971.

4.   Harish lf   Enterline Ht   Rosato fe : Sweat gland carcinoma :Ann surg. 174: 283-286, 1971.

5.  Bricoe ke  Grage t  Kenedy bj : Sustained Complete Remission
of Metastatic Sweat Gland Carcinoma .j am med assoc. 240:51-52, 1978.

6.   Morris dm  Sanusi d Lanehart wh: Carcinoma of Exocrine
Sweat Gland, Experience  with Chemotherapy , Autopsy findings in a patient
with  metastatic eccrine carcinoma , and a reveiw 
of the literature :j surg oncol. 31:26-30,1986.

7.   Neumann l  Sorensen ja  : Apocrine Carcinoma of the
Axillae . Case report: j plast reconstr surg. 23:157-158, 1989.

8.  Hainsworth jd  Johansen dh  Greco fa :Cisplatin-based combination
Chemotherapy in the Treatment of Poorly Differentiated carcinoma and Poorly
differentiated Adenocarcinoma of unknown primary site: result of a 12- year
experience . J clin oncol. . 10:912-922, 1992.

9.  Markman m: Metastatic Adenocarcinoma of unknown primary site, Analysis
of 245 patients seen at the Johns Hospital from 1965-1979: Med Pediatr      oncol. 10:569-574,1982.

10. Teo p  Shiu w   Tsao sy: A clinical study of adenocarcinoma
of unknown primary site in Hong Kong . Singapore med j. (571-573) 30,1989. 

Table:1              

Figure no.1 Section showing infiltrative carcinoma forming a malignant glandular
pattern. Apical snouts as indicated by the arrow was typical of apocrine differentiation
(Haematoxylin and eosin stain (200 X).

About authors:

Karthik Nair*, Vinit Ekshinge*, Pundalik
Pai*, Namdeo Jadhav*, Yuvraj Pawar**.

**Dr. D.Y.Patil Medical College, Kolhapur (MS).

*Bharati Vidyapeeth College of Pharmacy, Morewadi, Kolhapur (MS).

For Correspondence,

Namdeo Jadhav,
Lecturer in Pharmaceutics,
Bharati Vidyapeeth,
College of pharmacy,
Kolhapur
Pin- 416013.
Mobile:09422422123
O ffice:0231-2637286

nrjadhav18@rediffmail.com