Larry J. Copeland

Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer

A retrospective matched-control study was conducted to review our experience with FIGO stage III and IV epithelial ovarian cancer in patients referred after initial laparotomy and biopsy only. The study group comprised 22 patients; planned treatment was two to four cycles of chemotherapy, interval debulking surgery, six more chemotherapy cycles, and second-look laparotomy. Two control groups were matched with the study group according to FIGO stage, histologic type, and grade (2 or 3) and patient age +/- 5 years. The first control group (22 patients) had greater than 2 cm residual disease after initial surgery; their planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. The second control group (18 patients) was referred after initial laparotomy and biopsy only; their disease was immediately reexplored and debulked. Subsequent planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. All patients received cisplatin-based chemotherapy. Optimal cytoreduction to less than or equal to 2 cm was achieved for 77% of the study group vs 39% of the immediate-reexploration group (P = 0.02). Median survival times for the three groups were not different (16 vs 19.3 vs 18 months, respectively) (P = 0.58). Within the study group, patients who were optimally debulked survived significantly longer than those who were not (18.1 vs 7.5 months) (P = 0.02). Morbidity of the interval debulking procedure was acceptable. Study findings suggest that patients with bulky residual disease have a uniformly poor prognosis regardless of the timing of further surgery.

Prognosis of surgically determined complete responders in advanced ovarian cancer

From January 1971 through through December 1981, 246 patients with advanced (Stages III and IV) epithelial ovarian cancer underwent second‐look laparotomy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston. Eighty‐five of these patients had a complete response (negative second‐look laparotomy) following treatment with a variety of chemotherapeutic regimens. Three patients had also received irradiation. Patients were analyzed according to pretreatment characteristics (age, FIGO stage, ascites, pleural effusion, histologic grade, tumor type, type of surgery, residual tumor diameter, initial clinical status) and by the number of biopsy specimens taken at second‐look laparotomy. The probability of recurrence and the length of survival following a negative second‐look laparotomy are statistically related to these characteristics. Twenty of the 85 patients (24%) developed recurrent disease 5 to 32 months after laparotomy. The estimated 2‐ and 5‐year survival rates are 99% and 85%, respectively. Patients who achieve a surgically determined complete response have an excellent chance for long‐term survival.

Secondary cytoreductive surgery for recurrent epithelial ovarian cancer

Thirty patients with recurrent epithelial ovarian carcinoma who underwent secondary tumor-reductive surgery at M. D. Anderson Cancer Center were studied retrospectively. All had been initially treated by primary reductive surgery and postoperative chemotherapy and had a period of clinical remission of at least 6 months thereafter. Ninety percent of patients had grade 2 or 3 tumors. In 17 (57%), residual tumor volume was reduced to less than 2 cm. There were no postoperative deaths, but 40% of patients suffered postoperative morbidity, mostly prolonged ileus. Median survival after second surgery was 16.3-18 months for patients with residual tumor volume less than 2 cm and 13.3 months for those with residual volume greater than 2 cm (nonsignificant). When the second surgery followed the first by less than 18 months, survival was a median of 13.5 months after the second operation as compared with 19 months when the interval was 18 months or longer (nonsignificant). Twenty-two patients received postsurgical chemotherapy; only 11% of those who were evaluable responded. Although secondary tumor-reductive surgery for recurrent ovarian cancer is technically feasible, in the absence of an efficacious second-line medical therapy, its value is limited.

Bartholin gland carcinoma

Bartholin gland tumors are rare and management recommendations have been based on limited information. This report summarizes a 30-year clinical experience involving Bartholin gland carcinoma in 36 patients whose five-year survival rate was 84%. FIGO stages of the 36 tumors were stage I, nine; stage

Microscopic disease at second‐look laparotomy in advanced ovarian cancer

During the 11‐year interval from January 1971 to January 1982, 50 of 246 patients with advanced (Stage III and IV) epithelial ovarian carcinoma at second‐look laparotomy had biopsy or cytologic evidence of persistent microscopic carcinoma. The stage and grade profile include 46 Stage III and 4 Stage IV patients: 4 borderline, 9 grade 1, 20 grade 2, and 17 grade 3 patients. Following second‐look laparotomy, 4 patients received no further therapy, 45 received chemotherapy, and 1 received external radiation. No patient was lost to follow‐up, and the median interval off therapy was 24 months. Progressive or recurrent disease has manifest in 12 (24%). No recurrences have developed either in patients younger than age 40 or in patients with grade 1 tumors. Two patients died of leukemia, 1 died of heart disease, and 35 (70%) are alive with no evidence of disease. In patients developing recurrence, the median progression‐free interval was 17.5 months, with a range of 6 to 46 months. The median interval of survival following disease progression was 7 months. There was no evidence of progression at 2 years and 5 years in 81% and 70% of patients, respectively. The uncorrected 2‐ and 5‐year survival rates were 96% and 71%, respectively. The 5‐year survival rates for grades 1, 2, and 3 were 100%, 79%, and 36%, respectively. Other variables analyzed include number of positive foci, residual tumor volume at initial surgery, cytologic findings at second‐look laparotomy, type of chemotherapy, and number of courses of chemotherapy before second‐look laparotomy. In summary, patients with only microscopic evidence of disease at second‐look surgery have a good probability for extended survival.

Recurrent cervical carcinoma after radical hysterectomy

The characteristics of recurrent carcinoma following radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma are not well known. Disease recurrence was noted in 27 of 249 patients (11%) with stage IB cervical carcinoma who were treated with a primary surgical approach between January 1962 and December 1984. Fourteen recurrences (52%) occurred within 1 year of surgery, and 24 (89%) within 2 years. Patients with pelvic node metastases or adenocarcinoma had a significantly higher recurrence rate than did patients with negative nodes (33% vs 8%) or with squamous carcinoma (22% vs 8%). Seventeen patients (63%) had disease recurrence in the pelvis or vulva and 12 of these patients had recurrences within 1 year. Eight patients developed asymptomatic pelvic or vulvar recurrences, and all were diagnosed within 1 year. Ten patients (37%) developed recurrences outside the pelvis and 8 of these experienced recurrence after 1 year. Successful treatment after recurrence was independent of clinical or histopathologic parameters except site of recurrence. Eight of 15 patients (53%) who were treated with irradiation for a recurrence in the pelvis or vulva are free of disease 10 to 126 months (median, 48 months) after recurrence. Since irradiation can aid in salvaging patients with recurrent cervical carcinoma confined to the pelvis following radical surgery, clinical vigilance for this site of recurrence is emphasized.

Endodermal Sinus Tumor of the Vagina and Cervix

This report describes six patients with endodermal sinus tumor of the vagina and cervix, a polypoid friable tumor whose clinical presentation in girls younger than age 3 years simulates the presentation of sarcoma botryoides. In four of the six patients, the referring diagnosis was sarcoma botryoides. Five patients were treated with excisional surgery, and all six with chemotherapy. One patient with pulmonary metastases maintained a complete clinical response to vincristine, actinomycin‐D, and cyclophosphamide (VAC) for 11 months. This is the first report of such a response. One patient with a vaginal lesion remains clinically free of disease 2 years after local excision and 18 months of VAC chemotherapy. This is the first report of apparently successful therapy that allowed retention of childbearing potential. Four of the six patients have been disease‐free from 2 to 23 years. After examining the world literature, it is concluded that a combination of chemotherapy and surgery offers a reasonable prospect of cure with a minimum of serious side effects.

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vincristine, dactinomycin, and cyclophosphamide

Eighty patients with malignant nondysgerminomatous germ cell tumors of the ovary were treated with the combination of vincristine, dactinomycin, and cyclophosphamide (VAC) at The University of Texas M. D. Anderson Hospital and Tumor Institute. All patients underwent initial surgery: biopsy alone in 3 patients, unilateral salpingo‐oophorectomy in 48 patients, and bilateral salpingo‐oophorectomy with or without hysterectomy in 29 patients. Sixty‐six patients received VAC as primary postoperative therapy; 46 patients (70%) achieved a sustained remission. VAC produced sustained remission in 86% of patients with Stage I, 57% of patients with Stage II, 50% of patients with Stage III, and no patients with Stage IV disease. For patients with Stage I disease, survival rates did not differ among histologic groups, but in advanced disease, patients with immature teratoma did significantly better than the others. Four of the 20 patients who failed primary VAC therapy were salvaged with other therapies, and 8 of 14 treated with VAC after relapse or failure of other treatments were salvaged. Although VAC produces excellent results with very acceptable toxicity in patients with Stage I disease and advanced immature teratoma, survival of patients with other advanced histologic types has been disappointing. The authors are therefore treating this latter group with alternative therapy such as vinblastine, bleomycin, and cisplatin with the goal of achieving improved efficacy.

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin.

Fifteen patients with malignant nondysgerminomatous germ cell tumors of the ovary seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, were treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). All patients underwent initial surgery: biopsy alone in one patient, unilateral salpingo‐oophorectomy in ten patients, and bilateral salpingo‐oophorectomy with or without hysterectomy in four patients. Seven patients received VBP as primary postoperative therapy. One patient died of progressive disease at 15 months following diagnosis. The other six patients are alive without evidence of disease 9 to 47 months from the time of diagnosis. Eight patients received VBP as second‐line treatment; three patients had a complete response to therapy and are surviving disease‐free 41 to 71 months from the time of diagnosis. Four patients treated secondarily had a partial response; three of these patients subsequently developed progressive disease and died, while one patient survived after undergoing salvage therapy with an etoposide‐containing regimen. One patient had no discernible response to VBP therapy and died. The VBP regimen represents an aggressive, moderately toxic, short‐term combination regimen that has promising activity against malignant germ cell tumors of the ovary.

Second-look laparotomy in the management of malignant germ cell tumors of the ovary

From 1970 to 1985, 53 patients with malignant nondysgerminomatous germ cell tumors of the ovary underwent second-look laparotomy after initial surgery and combination chemotherapy. Twenty-two patients had immature teratoma, 15 had endodermal sinus tumor, 15 had mixed germ cell tumor, and one patient had embryonal carcinoma. Thirty-one of the neoplasms were stage I, four were stage II, 17 were stage III, and one was stage IV. Two patients received a combination of actinomycin-D, 5-fluorouracil, and cyclophosphamide; four patients received vinblastine, bleomycin, and cisplatin; 44 patients received vincristine, actinomycin-D, and cyclophosphamide; and three patients received a combination of the last two regimens. Second-look findings were negative in 52 patients and positive in one patient who was subsequently salvaged with further chemotherapy. One patient with stage I endodermal sinus tumor relapsed nine months after a negative second-look laparotomy and died. Two patients with negative findings subsequently died of leukemia. Of 53 patients undergoing second-look laparotomy, three are dead (one of cancer and two of leukemia), and 50 patients are surviving without disease. Although the precise role of second-look laparotomy in patients with malignant germ cell tumors is yet to be established, possible indications are discussed.