Advanced Squamous Carcinoma Research Articles

Phase II trial of vinblastine in patients with advanced or recurrent squamous carcinoma of the cervix

Phase II trial of vinblastine in patients with advanced or recurrent squamous carcinoma of the cervix

Phase II study of ifosfamide and mesna in patients with previously-treated carcinoma of the cervix

Thirty patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery and refractory to first-line chemotherapeutic agents were treated with ifosfamide in a dose of 1.2 grams/m2 IV daily for five days every four weeks and Mesna 300 mg/m2 IV every four hours for three doses daily for five days. One patient had an inadequate trial and two were inevaluable for response, leaving 27 patients evaluable for response. All but two patients had received prior radiotherapy and all but one prior cisplatin-based or cisplatin analog chemotherapy. Seventeen patients had prior surgery. All patients were Gynecologic Oncology Group performance status 0, 1, or 2. Partial responses were observed in three patients (11.1%), two with pelvic and one with extrapelvic disease. A 90% confidence interval for the true response rate is 4.5%-24.8%. Severe (grade 3 or 4) leukopenia and anemia were seen in nine and seven patients, respectively. Severe thrombocytopenia was not observed. Three patients had grade 3 or 4 neurotoxicity, and one had grade 3 renal impairment. Reversible alopecia was universal. This dose and schedule of ifosfamide and Mesna is active in patients with squamous carcinoma of the cervix failing platinum-based therapy. Phase II testing in untreated patients is currently underway.

Combined chemotherapy and radiotherapy in patients with advanced squamous carcinoma of the cervix (cis-platinum-bleomycin-vinblastine)

Combined chemotherapy and radiotherapy in patients with advanced squamous carcinoma of the cervix (cis-platinum-bleomycin-vinblastine)

Concomitant radiation therapy and chemotherapy in the treatment of advanced squamous carcinoma of the lower female genital tract

Twenty-three consecutive patients with advanced squamous carcinoma of the lower female genital tract were entered into a pilot study to determine the response rate and toxicity of a combination of intravenous cisplatin and 5-fluorouracil given concomitantly with radiation therapy. Twenty (87%) of the patients had a complete clinical response. Two patients (9%) had a partial response and one (4%) had stable disease. Nine (45%) of the complete responders have recurred with a median time to recurrence of 4 months. Seven (35%) had some component of local recurrence. The complete responders who have not recurred have been followed a median of 17 months. The acute toxicity was generally mild and there were no life-threatening acute complications. Three patients developed significant late complications. The response rate in this study was very high. The responses were usually prompt and dramatic, but often not sustained.

Phase II study of esorubicin (4'-deoxydoxorubicin) in advanced or metastatic squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.

Twenty-eight patients with advanced, measurable squamous carcinoma of the uterine cervix were treated with 62 courses of esorubicin at doses ranging from 20-35 mg/m2 every three weeks. All patients were evaluable for response and toxicity. All patients had received prior therapy including radiation therapy in 28, chemotherapy in 23, and surgery in 11. All patients were Gynecologic Oncology Group (GOG) performance status 0, 1 or 2. There were no responses seen. Severe (grade 3 or 4) leukopenia, thrombocytopenia, and anemia were seen in 13, 3, and 9 patients, respectively. Gastrointestinal toxicity as well as alopecia were the other adverse effects. Mucositis and phlebitis were not seen. Neither clinical congestive cardiomyopathy nor decrement in left ventricular ejection fraction was observed. Lack of response in association with moderate toxicity using this dose and schedule of esorubicin in squamous carcinoma of the cervix previously treated with chemotherapy makes further study as a salvage agent unwarranted.

Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced squamous bronchogenic carcinoma: A randomized study

Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced squamous bronchogenic carcinoma: A randomized study

Combined chemotherapy and radiotherapy in patients with advanced squamous carcinoma of the cervix ( cis-platinum-bleomycin-vinblastine)

In a pilot study, nine patients with advanced carcinoma of the cervix were treated with combination chemotherapy including cis-platinum, vinblastine, and bleomycin repeated at 3-week intervals for three courses followed by radiotherapy. Only one patient showed a partial response (reduction of tumor size more than 50%). There were no complete responses. Five of the nine patients have died from the disease with a median survival time of 20 months. These findings suggest that this particular combination of chemotherapy with radiotherapy does not have a significant effect in patients with advanced stage carcinoma of the cervix.

Chemotherapy of Advanced Head and Neck Squamous Carcinoma with Cisplatin, Fluorouracil and Bleomycin Administered in an Outpatient Schedule

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS greater than 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS less than 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.

Charged particle radiotherapy of selected tumors in the head and neck

For selected tumors in some sites in the head and neck region, charged particles such as protons or helium, carbon, neon and silicon ions provide improved dose distributions, higher tumor doses, and an increased chance of local control and prolonged survival. In tumors with “radioresistant” histologies, slow growth kinetics and/or hypoxic cells, the high-LET component of neon or silicon ions may also offer an added potential for increased effect on tumors. Sixty-seven (67) evaluable patients with tumors in the head and neck region having a histology other than squamous carcinoma received partial or full treatment with charged particles at the University of California Lawrence Berkeley Laboratory. The tumor sites included base of skull or cervical spine, salivary glands, paranasal sinuses, nasopharynx, and miscellaneous sites such as lacrimal gland, soft tissues of the neck, or thyroid. Follow-up ranges from 1–9 years with a mean of 36 months and a median survival (Kaplan-Meier technique) of 50 months. The actuarial local control rate is 60% at 24 months post-treatment. Thirty-one (31) patients with squamous carcinoma of various sites in the head and neck have also been treated using charged particle irradiation; local control was lower (11 of 31 pts) and survival shorter (mean: 9 months) in this group of patients with advanced squamous carcinoma.

Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin.

Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted.

Concurrent daily cisplatin and radiotherapy in locally advanced squamous carcinoma of the head-and-neck and bronchus

In order to exploit the cytotoxic and radiosensitising actions of cis-platinum, we have treated 35 patients with locally advanced squamous cell carcinoma of the bronchus or head-and-neck. Each patient underwent radical irradiation (60 Gy/30 fractions over 6 weeks) with daily low-dose intravenous cisplatin (10 mg absolute dose per day) administered within 30 min of each daily radiation fraction. Total dose of cisplatin was 300 mg over 6 weeks. Although treatment was complicated by nausea in almost all patients and transient renal dysfunction in the majority, 27 patients completed treatment and renal function returned to normal or near normal in almost all cases. There was no obvious enhancement of pulmonary or skin toxicity, beyond what would have been expected from treatment with radical radiotherapy alone. There were two treatment-related deaths from renal failure. The response rate was high: all patients achieved at least a partial response, and in head-and-neck sites, there were nine complete responders and seven partial responders. Of the initial 35 patients, of whom all but two had advanced inoperable disease, 11 have died and 21 remain in continuous remission, 8-120 weeks from the start of treatment (median 55 weeks).

Cisplatin--5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck.

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.

Laser Photodynamic Therapy for Inoperable Bronchogenic Squamous Carcinoma

Fifteen consecutive patients with advanced squamous bronchogenic carcinoma, most of whom had had radiotherapy, were given palliative photodynamic therapy, using either haematoporphyrin derivative or dihaematoporphyrin ether to light sensitize their tumour. All tumours responded to treatment by subsequent light at 630 nm and in the 12 patients where adequate tumour illumination was achieved there was complete clearing of the bronchus in three and partial (more than 50 per cent clearing) in the remaining nine, with relief of haemoptysis and/or breathing obstruction. One patient with recurrent tumour in a pneumonectomy stump after radiotherapy has remained disease-free for over two years since photodynamic therapy. The main complications were temporary skin light sensitization reaction in three, infection after reaeration of lung tissue in two, and transient but severe worsening of breathing obstruction in two.

The influence of hematogenous and serosal metastases on advanced (FIGO IIA-IVB) squamous cell carcinoma of the cervix.

Of 120 patients with FIGO stage IIA-IVB squamous cell carcinoma of the cervix treated with standard radiotherapeutic techniques, 41 (34.2%) relapsed with hematogenous or serosal metastases. Development of such metastases was individually associated with patient age less than or equal to 55, bilateral bulky parametrial extension, and histologically positive paraaortic nodes. Poor histologic differentiation exerted significant negative influence only in patients age less than or equal to 55. Neither surgical staging nor vascular injury predisposed to hematogenous dissemination. Radiotherapy techniques differed only in increased time to completion, from 84 to 100 days in clinical IIB and IIIB patients developing metastases. Local or regional pelvic recurrences, although associated with an increase in hematogenous or serosal metastases, were not accompanied by concomitant relapse in extrapelvic nodes. Twenty-six of 41 metastases were limited to single organ systems, with pulmonary sites most common (43.9%). A direct (non-nodal) route of hematogenous dissemination of 31% was documented within clinical stages IIA and IIB. One hundred percent concordance between bilateral bulky parametrial involvement and positive pretreatment paraaortic nodes occurred in clinical stage IIIB and IVA patients with metastatic relapse. Our data from the period 1976-1985 do not substantially differ from earlier reports on the incidence or distribution of hematogenous or serosal metastases, despite our implementation of contemporary local/regional radiotherapy prescriptions. The potential for hematogenous and serosal metastases in high-risk patients with advanced squamous cervical carcinoma merits consideration of alternative treatment protocols and precise definition of the role of pretreatment surgical staging procedures.

The use of concomitant chemotherapy and radiotherapy prior to surgery in advanced stage carcinoma of the vulva

Six cases of primary advanced squamous carcinoma of the vulva were treated with concomitant chemotherapy and radiotherapy (C + RT). In five patients it was given in preparation for surgery. The radiation was delivered to the whole pelvis in 10 equal daily fractions of either 2.0 or 2.5 Gy. Mitomycin C (10 mg/m 2) was given on Day 1, and 5-fluorouracil (1000 mg/m 2) was given daily from Days 1 to 4, inclusive. All six patients had satisfactory early tumor response. Three patients received one course of C + RT and three were given two courses. One patient died suddenly of unknown causes 6 days after completing the C + RT. One patient with fixed groin nodes was treated with palliative intent. She maintained a complete local response but died 6 months later of liver metastases. The remaining four patients underwent surgery without healing complications and are alive with no evidence of disease at 1, 4, 14, and 26 months. In our experience vulval carcinomas can be reduced in size and extent by prior chemotherapy and radiotherapy and require less extensive surgery.

Irradiation with misonidazole and hyperbaric oxygen: Final report on a randomized trial in advanced head and neck cancer

One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease.

A phase II study of CHIP in advanced squamous cell carcinoma of the cervix (a Gynecologic Oncology Group Study).

The Gynecologic Oncology Group (GOG) conducted a Phase II trial of CHIP, cis-dichloro-trans-dihydroxy-bis-(isopropylamine)-platinum IV, in patients with measurable advanced squamous cell carcinoma of the cervix. No prior therapy with cytotoxic drugs was permitted in patients entered into this trial. All patients had a GOG performance status of 2 or better. CHIP at a starting dose of 230 mg/m2 was administered as a 30-minute IV infusion. Dose escalation was permitted to a maximum of 300 mg/m2. Treatments were repeated every four weeks until disease progressed or until toxicity prohibited further therapy. Thirty-six evaluable patients were entered between January and July, 1984. Of these, 34 were evaluable for response. Four complete and three partial responses were observed (response rate 20.6%). No neurotoxicity was noted and only mild and reversible nephrotoxicity was reported. Grade 3 gastrointestinal toxicity was reported in twenty patients (56%). Dose-limiting toxicity was myelosuppression. CHIP is an active agent against squamous cell carcinoma of the cervix and appears to be less neurotoxic and nephrotoxic than cisplatin. Gastrointestinal toxicity was moderate and appears equal to that seen with cisplatin at a dose of 50 mg/m2 given as a rapid IV infusion and more toxic than an equivalent dose of cisplatin administered over 24 hours. Randomized studies comparing CHIP and cisplatin are indicated to better define the relative therapeutic indices of these two compounds in the treatment of advanced squamous carcinoma of the cervix.

Multidisciplinary treatment of advanced squamous carcinoma of the head and neck.

Advanced squamous carcinoma of the upper aerodigestive tract continues to be a therapeutic challenge. With recent advances in chemotherapy, systemic treatment has been used in an attempt to improve treatment results produced by radiation therapy and/or surgery. Such multidisciplinary experimental approaches have given new hope for cure in stage III and stage IV disease, but have reopened old questions as to the natural history and underlying biology of this disease. Multidisciplinary treatment, whether synchronous or sequential, appears to improve survival for stage III and stage IV patients achieving a complete response to chemotherapy plus irradiation. The role of surgery or radiotherapy for control of primary or nodal disease remains unchanged and is an essential component of all curative treatment plans.

The effectiveness of multidrug treatment by bleomycin, methotrexate, and cis-platinum in advanced vaginal carcinoma

A case of a female with advanced squamous carcinoma of the vagina is presented. Complete disappearance of the primary tumor and involved inguinal lymph nodes was achieved with three courses of the cis-platinum-containing chemotherapy regimen BMP administered prior to radiotherapy. The encouraging result obtained warrants the use of this combined treatment modality in other patients.

Cisplatin and doxorubicin. An effective chemotherapy combination in the treatment of advanced basal cell and squamous carcinoma of the skin.

Eleven patients with advanced basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin were treated with cis-diamminedichloroplatinum II (cisplatin) and doxorubicin. Seven patients had prior surgery and six of these seven had prior radiation therapy. All patients had an adequate trial of chemotherapy. One patient received a second course of chemotherapy after relapse. Responses were seen in 10 of 12 (87%) of chemotherapy courses, and 5 of 11 patients (46%) have an unmaintained complete remission lasting 2 to 31 months. Toxicity was acceptable and consisted primarily of gastrointestinal side effects. These results indicate the combination of cisplatin and doxorubicin has significant activity in both advanced BCC and SCC of the skin. In addition, a portion of patients treated with the combination achieve a long-term unmaintained disease-free state.