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The first conference on concomitant infusion chemotherapy and radia­ tion therapy was organized with the intention of bringing together some of the investigators who have tested, during the last few years, the hypo­ thesis that continuous infusion chemotherapy could modulate the cytotoxic effect of radiation therapy to the point of having a strongly additive, if not synergistic activity on certain malignant tumors. This volume represents the detailed proceedings of this conference presented in a way that offers the reader a review of the on-going re­ search in the field. We have stressed a number of subjects from basic biologic research and influence of cell kinetics to the practical methods of drug delivery systems and early clinical experiences. The rationale for this new type of combined modality therapy has been presented by some of its pioneers. Early clinical investigations as well as the preliminary data of many that have not yet completely matured have also been included. The reader should look at these data with some reser­ vations. Ultimately, these results must be confirmed by larger prospective randomized studies with proper controls before becoming accepted as the treatment of choice in locally advanced tumors.

Inhaltsverzeichnis

Frontmatter

Protracted Administration of Antineoplastic Chemotherapy Agents

Frontmatter

Principles and Therapeutic Applications

Theoretical, Clinical, and Pharmacokinetic Aspects of Cancer Chemotherapy Administered by Continuous Infusion

Most anti-cancer drugs produce toxic side-effects at the doses used for treatment. This low therapeutic index, or ratio between therapeutic and toxic doses, has prompted various approaches towards increasing the selectivity of cancer chemotherapy. Perhaps the most successful of these has been the use of combination chemotherapy, which increased the therapeutic ratio by combining drugs with non-overlapping side-effects and in some cases lowering individual doses. This approach over the last twenty years has resulted in the cure of several types of cancer (leukemias, Hodgkin’s and non-Hodgkin’s lymphomas, germ cell cancers). The use of drugs in combination is not curative for most human solid tumors, however, and in fact may increase toxicity without increasing therapeutic efficacy for tumors which are refractory to the drugs employed.

Branimir Ivan Sikic

Pharmocology and Therapeutic Efficacy of Bleomycin Administered By Continuous Infusion

Bleomycin was isolated by Umezawa1. It has been in clinical use for more than 15 years. The initial clinical studies performed by Ichikawa, et al2 demonstrated useful activity in the squamous carcinomas. Subsequent studies have demonstrated useful therapeutic activity in lymphomas and germ cell tumors3–5.

Irwin H. Krakoff

Continuous-Infusion Adriamycin

The use of adriamycin is frequently limited by the development of a cumulative-dose-dependent cardiomyopathy, which increases substantially in incidence at doses ≥550 mg/m2. To avoid the potential development of fatal refractory congestive heart failure (CHF), dose limitation to 450–550 mg/m2has been recommended by a variety of authors.1–3Since an oncologist may not wish to stop treatment of an individual patient at an arbitrary level, a considerable investment of time and resources has been made in an effort to extend the use of adriamycin or develop analogs with diminished cardiotoxicity to accomplish the same aim.

Robert S. Benjamin, Sant P. Chawla, Gabriel N. Hortobagyi, Michael S. Ewer, Bruce Mackay, Sewa S. Legha, C. Huberto Carrasco, Sidney Wallace

5-Fluorouracil Plus Thymidine or Leucovorin by Continuous I.V. Infusion in the Treatment of Advanced Colorectal Carcinoma

5-Fluorouracil (FUra) has been the drug of choice in the treatment of colorectal cancers (1,2), and it is widely utilized in a variety of other malignancies (3). FUra exerts its antiproliferative effect following metabolic activation to various nucleotides (Chart 1). 5-Fluorouridine triphosphate (FUTP), due to its resemblance with uridine triphosphate (UTP), is incorporated into RNA (4–7); the consequence of this incorporation is the production of fraudulent mRNA, rRNA and tRNA which can ultimately cause cell death. The other proposed mechanism for FUra cytotoxicity is the inhibition of thymidylate synthetase (dTMP-S) by 5-fluorodeoxyuridine monophosphate (FdUMP) (8–11), leading to decreased thymidine triphosphate (dTTP) pools and to inhibition of DNA synthesis. The biochemical mechanism by which FdUMP binds to the dTMP-S involves a cofactor, N5,10methylene tetrahydrofolic acid (N5,10CH2FH4). Santi et al. have calculated that the dissociation constant (Kd) of the ternary complex FdUMP-dTMP-SN5,10CH2FH4, is of the order of 5×10-11M. In absence of the reduced folate cofactor, FdUMP binding to dTMP-S is relatively weak, with a Kd of about 10-5M (9). An additional proposed mechanism of cytotoxicity of FUra is its incorporation into DNA (12–15). To date, little is known about the biological significance of this finding.

Fabio Trave, Youcef M. Rustum

Epipodophyllotoxin and Cisplatin on Continuous Infusion Schedules

The Epipodophyllotoxins, VP16-213 and VM26, and the heavy metal cytotoxic agents, Cisplatin and its analogs, Spirogermanium and Gallium, represent two classes of agents which in clinical trials are traditionally delivered on an intermittent bolus schedule. Extensive clinical reviews of the clinical trials employing these agents have not emphasized the continuous infusion schedule (1–3). In fact, the thrust has been directed toward maximizing the dose of delivery on an intermittent bolus schedule to increase therapeutic effects (4,5). Such has been the traditional approach to cancer chemotherapy in general based upon the concept of the dose-response relationship developed in experimental tumor systems and upon practical issues involving patient convenience and outpatient delivery. Such precepts have been the basic tenets for the day one and eight schedule for such programs as MOPP chemotherapy for Hodgkin’s disease and the CMF program for breast cancer.

Jacob J. Lokich

Biodegradable Starch Microspheres (Spherex), a Clinically Useful Medical Device for Combined Intra-Arterial Chemotherapeutic Treatment of Primary and Metastatic Cancers of the Liver: The Potential Clinical Value for Spherex in Regionalized Immunotherapy, Hyperthermia and Radiation Protection

Spherex is a medical device which produces controlled occlusion of arterial vessels for a half life of 15′, governed by serum amylase digestion. The purposes of this study were to determine the feasibility and toxicity of the use of Spherex with standard chemotherapeutic agents for the treatment of unresectable cancers of the liver.Twenty two patients with advanced cancer involving the liver were treated with hepatic arterial (HA) chemotherapy mixed with 900mg of 45µ biodegradable starch microspheres (Spherex-Pharmacia) in a phase II study of Spherex combined with standard chemotherapy. Thirteen patients were treated repeatedly via permanent HA catheters placed operatively using subcutaneous ports whereas 9 patients received their treatments through percutaneously femoral placed HA catheters.Seven patients of 22 treated clearly showed regression of liver metastases with 4 showing improvement in quality of life. All but one patient studied had >50% tumor liver replacement. Twelve colorectal patients received 5FU 600mg/m2 day 1 and mitomycin, 10mg/m2 day 3 in 28 day cycles. Adriamycin, 30mg/m2, was used to treat one breast cancer patient; and 2 hepatoma patients with a significant partial remission of 9 months in the patient with breast cancer. Five patients received BCNU 100–200mg; 3 with melanoma with one dramatic response that lasted 7 months; one epidermoid carcinoma responded to 2 courses of BCNU and one of thiotepa with dramatic regression and clinical improvement and is still alive at 10 months. One patient, a systemic FAM failure, has responded to 5FU/mito and 5FU alone x 3 courses. Eight patients had one course, 3:2, 3:3, 4:5, 1:5, 1:7, 1:8, 1:14 of Spherex/chemotherapy.Mild hematologic toxicity was present in only one patient and only 1 of 22 patients had a complication with duodenitis from improper catheter placement. Transient pain in liver and nausea and vomiting were the major toxicities seen.From our Phase II study, we feel that Spherex chemotherapy can be repeatedly administered via the HA as a convenient palliative approach to liver metastatic or primary disease. The advantages of Spherex HA occlusion combined with chemotherapy relate to the fact that 85–95% of the blood supply to metastatic carcinoma of the liver is of HA origin and Spherex achieves a tumor ischemia combined with an increase in chemotherapy concentration to the HA bed with minimal systemic toxicity.This study demonstrates the safety and convenience of Spherex/chemotherapy combinations, but the therapeutic advantages of Spherex over other forms of hepatic arterial occlusion or chemotherapy can only be inferred unless a larger controlled or comparative study is undertaken.Spherex occlusion has also been used experimentally in Sweden to produce transient ischemia of bowel and peripheral limbs to protect target organs from radiation injury during the occlusive period. Hyperthermia to liver metastasis can be regionally enhanced during Spherex administration and this approach deserves study.

George Parker, William Regelson

Selective Therapy of Hepatic Cancers Using Microspheres

Regional chemotherapy is based on the premise that many chemotherapeutic agents display a steep dose response for toxicity and for therapeutic effect. Regional chemotherapy administration represents a means to generate increased drug exposure in the region where the tumor resides, while maintaining a lower drug exposure at the level of dose-limiting normal host tissues elsewhere in the body. Thus, even in circumstances where systemically administered chemotherapy is relatively ineffective, regional chemotherapy may improve the likelihood of response by the generation of much greater drug exposure. With sufficient regional selectivity, dose-limiting toxicity should be manifested by the normal tissues of the region infused and not by tissues elsewhere in the body. In this regard, regional chemotherapy has similarities to radiation therapy, but may be more selective in those situations where tumor and normal tissue in the treated region differ significantly in intrinsic drug sensitivity and blood supply.

John W. Gyves

Clinical Studies

Preliminary Results of a Randomized Study of Intrahepatic Infusion versus Systemic Infusion of FUDR for Metastatic Colorectal Carcinoma

Development of a totally implantable infusion pump produced a renewed interest in hepatic infusional therapy. An initial study employing this pump and continuous hepatic infusion of FUDR produced an 83% response rate1. However, further work with this method brought the mean response rate down to 59%2which, however, is still higher than the mean response rate obtained with systemic chemotherapy.

Nancy Kemeny, John Daly

COPBLAM: Infusion Chemotherapy for Large Cell Lymphoma

Early in 1977, a new combination chemotherapy program was initiated at the New York Hospital-Cornell Medical Center for large cell lymphoma (LCL). This program, known as COPBLAM: {cyclophosphamide, Oncovin, (vincristine), prednisone, bleomycin, Adriamycin, Matulane (procarbazine)} was an intensive multidrug regimen designed to maximize tumor cell kill1. Unique to this treatment for LCL was the incorporation of then novel concepts and features which were as follows: 1)Dosage escalation provisions for two major drug components (cyclo-phosphamide, Adriamycin) appropriate to patient tolerance, thereby allowing fullest implementation of these agents. Protocols in the past had provided dosage reduction schedules when treatment proved too intense, but few had ever contained provisions for increasing treatment intensity, notwithstanding the steep dose-response relationship of these drugs2.2)Treatment cycles of 21 days, in contrast to the customary monthly schedules used in the past. Toxicity from both cyclophosphamide and Adriamycin is usually ameliorated in this interval, and shorter cycles provided for further intensification of treatment2.3)The use of six drugs rather than the customary four or five, all putatively non-cross-resistant with differing mechanisms of action. Procarbazine was added to the standard BACOP (bleomycin, Adriamycin, cyclophosphamide, Oncovin, prednisone) combination because of its ability to cross the blood brain barrier. Its previous incorporation in the COP (cyclophosphamide, Oncovin, prednisone) regimen to form the C-MOPP (cyclophosphamide, Oncovin, procarbazine, prednisone) program greatly augmented the cure rate3.4)The fuller use of nonmyelosuppressive agents, particularly vin-cristine, prednisone and bleomycin, of which the latter was given at day 14, allowing further tumor treatment in the face of nadir blood counts.

Morton Coleman, D. Barry Boyd, Bernard Bernhardt, Gary Gerstein, Samuel Kopel

Adriamycin Continuous I.V. Infusion for the Treatment of Childhood Hepatic Malignancies, Toxicity, and Efficacy: A Pilot Study Childrens Cancer Study Group, Los Angeles, California

The beneficial effect of adjuvant chemotherapy to surgery in children with resectable hepatoblastoma and hepatocellular carcinoma has been documented. However, the same chemotherapy regimens have failed to improve survival for patients with unresectable disease.

Jorge A. Ortega, Williams Woods, James Feusner, Gregory Reaman, Beverly Lange, G. Denman Hammond

An Uncontrolled Phase II Study of Constant Infusion Vincristine-Adriamycin

The combination of adriamycin and vincristine administered as bolus injections have antitumoral activity in pediatric cases; however there are no published reports of concomitant constant infusion vincristine and adriamycin. Due to their short serum half-life, it seems reasonable that an improvement in their therapeutic index might occur if these drugs were given as a continuous infusion. In support of this, there is published evidence of reduced cardiotoxic effects in adults for adriamycin when it was administered as a constant effusion (1). We considered it reasonable to evaluate the clinical effects of the combination administered as a constant infusion in patients who were considered refractory to these same drugs given as bolus injections.

L. Helson, M. A. Castello, E. Arenson, L. Steinherz, S. Groshen

Low-Dose Ara-C by Continuous Infusion in the Treatment of Acute Non-Lymphocytic Leukemia (ANLL) and Myelodysplastic Syndrome (MDS)

Thirteen patients with acute non-lymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS) were treated with low-dose cytosine arabinoside (Ara-C) 20 mg/m2/day by continuous intravenous infusion for 21 days. Seven patients attained complete remissions (CR) and two patients had partial remissions (PR). Two patients required two courses of treatment before attaining CR. Two of four patients with abnormal cytogenetics also achieved complete response with reversion of cytogenetic abnormalities to normal. All patients who responded showed profound pancytopenia with marked hypoplasia of bone marrow. The universal occurrence of pancytopenia and reversion of cytogenetic abnormalities to normal suggests that low-dose Ara-C is cytotoxic and may not act as a differentiating agent.

Farida Chaudhri, Steven L. Allen, Philip Schulman, Willi Kreis, Daniel R. Budman, Lora Weiselberg, Vincent Vinciguerra

The 5-Day Continuous Infusion of Cis-Platinum: An Update on Toxicity Pattern

Cis-Diamminodichloroplatinum (II), or DDP, has been shown to be an effective agent in the treament of various neoplastic diseases. The drug has been usually administered in high intravenous (IV) bolus dose, or rapid infusion. By these schedules, the toxicity of DDP included severe nausea and vomiting, nephrotoxicity, mild to moderate myelosuppression, and hearing loss1. Renal and gastrointestinal toxicities were dose-limiting and constituted major obstacles to prlonged therapy. Although nephrotoxicity was partially ameliorated by fluid and mannitol diuresis2, it remains a major impediment of long-term treatment. Also, in several studies, nausea and vomiting were so severe that many patients refused to continue treatment.

P. Salem, M. Khalyl, K. Jabboury, L. Hashimi

Long Term Appraisal of the Lemon-Foley Method of Chemotherapy of Solid Tumors of the Gastrointestinal Tract

One of the most difficult problems in the clinical judgement of cancer patients is the determination of the effectiveness of any treatment modality. This is particularly apparent in the evaluation of solid malignancies of the gastrointestinal tract. In 1966, Drs. Lemon and Foley proposed the slow infusion of one gram of 5FU for periods of eight hours daily for 14 days followed by weekly bolus I-V injections of .5 grams 5FU in l0cc of dilutent. They felt that this method was not only effective but also avoided the frequent severe iatrogenic complications of current anti-neoplastic chemotherapy.

Donald Steinberg

Antineoplastic Effects of Radiation Therapy and Chemothrapy by Continuous Unfusion

Frontmatter

Principles and Therapeutic Applications

Theoretical Basis and Clinical Applications of 5-Fluorouracil as a Radiosensitizer

During the past 5 years several institutions have combined the anti-metabolite 5-F1uorouraci1 (5-FU) and radiation in the treatment of various human cancers. The results of these studies are thus far uniformly promising but as yet no randomized investigations have been conducted. The stimulus to these pilot studies came from two disparate sources, The first was the empiric observation by Nigro et al (23) that an infusion of 5-FU (combined with Parfiromycin or Mitomycin C), coupled in part with radiation, led to rapid pre-operative regression of squamous anal cancer. These results led to an application of this type of pre-operative program to other cancers (15, 17, 20, 26).

John E. Byfield

Treatment of Hepatic Metastases from Gastrointestinal Primaries with Split Course Radiation Therapy and Concomitant Infusion 5-Fluorouracil

Metastases are detected in the liver in almost one third of cancer patients autopsied16and a 60–70% incidence3 is not unusual for metastatic large bowel cancer, Taylor21 reported progressive hepatic insufficiency as a cause of death in 25% patients who had radical resection for colorectal cancer.

M. Rotman, I. Bhutiani, A. Kuruvilla, K. Choi, J. Rosenthal, A. Braverman, J. Marti

Combined Modality Therapy With 5-Fluorouracil, Mitomycin C and Radiation Therapy for Squamous Cell Cancers

The eradication of epidermoid cancers of the anal canal by an empirically developed program of concurrent radiation, 5-Fluorouracil (5FU), and Mitomycin C (MTC), was described by Nigro, Vaitkevicius and Considine in 1974. The rapid and complete tumor response obtained in the first three patients encouraged these investigators, and subsequently others, to evaluate the combination in patients with squamous cell carcinomas in different sites. It is perhaps fortuitous that epidermoid anal carcinomas were treated first, for the results in that site have generally been the most striking, and even then some authors have questioned whether similar results could not have been achieved with simpler regimens.

B. J. Cummings, T. J. Keane, A. R. Harwood, G. M. Thomas

Treatment of Bladder Carcinoma with Concomitant Infusion Chemotherapy and Irradiation

In 1983 carcinoma of the urinary bladder was responsible for over 10,000 deaths in the United States1. Despite advances in treatment and detection of the disease, this death rate has remained virtually unchanged for the last 30 years. Transurethral resection, partial cystectomy and interstitial implant are appropriate treatments for low grade, low stage tumors, while pre-operative irradiation followed by planned cystectomy is the accepted modality of treatment for high stage, deeply invasive carcinomas. Patients who demonstrate complete response in the surgical cystectomy specimen carry a better prognosis2,3,4,5. Blandy in 1980, showed that patients achieving complete response within 6 months of curative irradiation had a 5 year survival rate of 56%2. Therefore, if the complete response rate can be improved then hopefully this will translate into prolonged survival.

M. Rotman, R. Macchia, M. Silverstein, K. Choi, J. Rosenthal, A. Braverman, H. Aziz

A Urologist’s Viewpoint: Treatment of Invasive Bladder Cancer by the XRT/5FU Protocol

Primary transitional cell carcinoma (TCC) localized to the urinary bladder occurs as: A, carcinoma in situ (CIS), B, superficial disease penetrating the basement membrane but not invasive of detrusor muscle, C, disease invasive of the detrusor muscle, or a mixture of these. CIS is most frequently treated with intravesical chemo or immunotherapy. Radical cystectomy is utilized for treatment failures. Superficial disease is treated by transurethral resection (TUR-BT) followed by intravesical chemo or immunotherapy.

Richard J. Macchia, Gobind Laungani

Concomitant Radiation Therapy and Doxorubicin by Continuous Infusion in Advanced Malignancies - a Phase I-II Study - Evidence Of Synergistic Effect in Soft Tissue Sarcomas and Hepatomas

The current lack of effective therapy against most malignant tumors in advanced stages is due, primarily, to its lack of specific cytotoxicity for neoplastic cells.

C. Julian Rosenthal, Marvin Rotman, Inder Bhutiani

CIS Platin By Continuous Infusion with Concurrent Radiation in Malignant Tumors (A Phase I-II Study)

Cis-Diamminedichloroplatinum II (Cis-DDP or Cisplatin) the first of the group of platinum coordination complexes used effectively against some human malignancies, was found, since 1974, to potentiate irradiation effects on experimental tumors (1). Since 1977 Douple and Richmond (2–4) have concluded, based on a number of experimental studies on E coli bacterium (5), V-79 Chinese hamster cells, mouse mammary adenocarcinoma, etc. that cisplatin sensitizes hypoxic cells to radiation, increases DNA susceptability to radiation damage and at the same time inhibits the radiation induced repair of potentially lethally damaged DNA. A convincing experimental demonstration of the radiosensitizing effect of cisplatin was obtained by Kyriazis et al (6) on a human bladder carcinoma implanted in nude mice. The mice receiving both modalities of treatment had a statistical significantly longer response and survival than those receiving radiation alone. Other experimental data suggested that the Cisplatin-Radiation interaction was enhanced when radiation was administered in multiple fractions (7) and that cisplatin could be possibly more effective when administered by continuous infusion because even so it is a phase cycle nonspecific drug, DDP acts preferentially on the G1 phase (8). On clinical grounds preliminary studies (9–11) of cisplatin-radiation combination have used only bolus i.v. administration of the drug. While indicating a favorable trend they have been inconclusive in proving its radiosensitizing effect.

C. J. Rosenthal, M. Rotman, K. Choi, J. Sand

Clinical Studies

Combination of Radiation with Concomitant Continuous Adriamycin Infusion in a Patient with a Partially Excised Pleomorphic Soft Tissue Sarcoma of the Lower Extremity

It has been known for many years from the observation of acute and chronic normal tissue damage in patients receiving multimodality therapy that the effects of radiation may be enhanced in the presence of many chemotherapeutic agents (1,2,3). This observation has naturally led to many attempts to use these agents to sensitize tumors to radiation and thus obtain better local control and survival than would be possible with radiation alone. Ideally the agent used should itself be active against the tumor being treated in order to obtain the benefit of direct cell killing as well as that of radiation sensitization. The usual method of delivery of the chemotherapeutic agents has been by IV bolus, however, Byfield et al (4) and Rotman, Rosenthal et al (5) among others have done extensive investigation of the use of concomitant continuous IV infusion Chemotherapy for radiation sensitization. The advantage of this mode of delivery as IV bolus is that the tumor is exposed to the chemotherapeutic agent for a longer period of time and the toxicity is diminished although a higher dose of agent is used (6).

S. Turner, R. Shetty, H. Gandhi, A. Latyshevsky, J. Korzis, R. Yaes

Treatment of Recurrent Carcinoma of the Paranasal Sinuses Using Concomitant Infusion CIS-Platinum and Radiation Therapy

Radiotherapeutic control of squamous cell carcinoma extending to or destroying adjacent bone is unlikely without surgical resection. Successful treatment even with combined modality therapy is unlikely when tumor extends beyond the confines of the adjacent bone. Such is the case in advanced carcinomas of the paranasal sinuses. Unfortunately, paranasal sinus tumors often remain asymptomatic until advanced with an average delay of six months between the onset of symptoms and the start of treatment. (1)

M. Rotman, K. Choi, S. Isaacson, J. Rosenthal, A. Braverman, J. Marti

Hepatic Artery Infusion (HAI) For Hepatic Metastases in Combination with Hepatic Resection or Hepatic Radiation

Hepatic metastasis is the major cause of death in advanced cancer of the colon and rectum. Survival after the diagnosis of liver metastases ranges from 3–12 months (4,6,7,14). Various modes of therapy have been attempted with only partial success. Resection of isolated hepatic metastases has yielded a 15–30% five year survival (1,3,12,13). Intraarterial infusion chemotherapy using an external catheter has been performed by several investigators with response rates of 50–60% (2,8,15,16). Survival, however, averages only 8 1/2 to 10 months, which is not significantly different from historical controls. The major problem with this therapy appears to be technical difficulties related to the external pump and catheter and the resultant necessity to terminate the intra-arterial chemotherapy (10). Radiation of the liver as an adjunct to hepatic infusion therapy has been utilized (5).

H. W. Merrick, R. R. Dobelbower, J. F. Ringleint, R. T. Skeel

Phase II Study of Simultaneous Radiation Therapy Continuous Infusion 5-Fu and Bolus Mitomycin-C

The combination of radiation therapy with a continuous infusion of 5-Fluorouracil and bolus injection of Mitomycin-C has been successful in the treatment of carcinomas of the anal canal and also squamous-cell carcinomas of the female genitalia and of the head and neck. One hundred and ten patients with a variety of carcinomas selected because of their expectedly poor response to standard treatment have been treated at our institution with a combination of radiation and chemotherapy. Best results were obtained in patients with squamous-cell carcinomas of the anal canal, esophagus, head and neck and cervix, with 70% of evaluable patients demonstrating a complete response and 21% showing a partial response. Patients with adenocarcinomas of the gastrointestinal tract faired poorly with only a 61% response, most of them partial. While this particular combination of chemotherapy and radiotherapy appears promising in squamous cell carcinomas of the head and neck, esophagus, anal canal and uterine cervix, results in other malignancies appear far less adequate and suggest that other combinations will have to be examined.

Oscar A. Mendiondo, Lawerence C. Maguire, William D. Medina, John D. Cronin

Cancer of the Esophagus — Medical University of South Carolina Pilot Study

Cancer of the esophagus is a rare neoplasm accounting for 2% of all cancer deaths each year.1 The survival remains poor despite improved staging, post-operative care, and adjuvant therapy. Our previous experience is summarized in Table 1. During the period 1940–1951, the majority of the patients were treated surgically when considered operable. The two-year survival remained consistently less than 1% during the decade. Throughout the next twenty-six years, radiation therapy was added to the treatment plan, first as a definitive treatment and later as an adjuvant to therapy. Cures with any modality remained uncommon.

J. H. Jenrette, R. D. Marks, E. F. Parker, R. H. Fitzgerald

Continuous Infusion VP-16, Bolus Cisplatin, and Simultaneous Radiation Therapy as Salvage Therapy in Small Cell Bronchogenic Carcinoma

VP-16 is regarded as one of the most active single agents in small cell bronchogenic carcinoma (SCBC). As second line therapy response rates have ranged from 0–40% with a cumulative series response rate of 12% in 381 patients.(1–10)the importance of VP-16 scheduling is suggested by invitro data revealing enhanced cytotoxicity after prolonged exposure and clinical data showing the benefit of frequent, daily schedules over weekly administration.(11,12)Cisplatin as second line therapy for SCBC has demonstrated significant activity in 8 of 54 patients.(13,14,15)

K. Rowland, P. Bonomi, S. Taylor, S. Maffey, S. Reddy, M. S. Lee

Concomitant Radiation, Mitomycin C And 5 Flourouracil Infusion in Gastrointestinal Cancer - A Preliminary Report

For a decade, concomitant radiation and chemotherapy with 5-Fluoro- uracil and Mitomycin C has been used in treating carcinoma of anal canal with favourable results (Nigro1, Cummings2, Byfield3). Similar encouraging results have been reported with esophageal carcinoma (Byfield4, Franklin5, Keane6). To date, this combination therapy has been used chiefly in squamous cell carcinoma. It’s efficacy in adenocarcinoma is not well documented, though felt to be ineffective by some authors. Wassif7 has employed similar combination in patients with advanced stages of rectal carcinoma, and reported local response rate of 79–85%.

A. Chan, A. Wong, K. Arthur

Techniques for the Administration of Chemotherapy Agents by Continuous Infusion

Frontmatter

Procedures for the Use of Implantable and External Pumps for Continuous Infusion Chemotherapy

The administration of chemotherapeutic agents is now being done more frequently on an outpatient basis which contributed to the improvement of the quality of life of cancer patients; this has become possible since small portable pumps were developed. The use of two of these pumps, one implantable (Infusaid), the other external (Cormed) will be described in this article. They are herein described, because of the author’s familiarity with their use for more than three years at the Chemotherapy Unit of Downstate Medical Center, Brooklyn, N.Y. Several other types of portable pumps are also available and apparently equally effective, but the author did not have the opportunity to use them.

Bettina Bentley Willis

Central Line Catheter Care: The Nurse and the Patient’s Perspective

Vascular access in patients requiring antineoplastic drugs is often a serious and challenging problem. Chemotherapy protocols frequently involve drugs that are severely irritating to peripheral veins. As a result patients receiving I.V. antineoplastic drugs over months or years experience thrombosis, sclerosis and destruction of available surface veins. The search for a suitable vein can become a painful ordeal for the patient, a time-consuming and disruptive endeavor for the physician and oncology nurse.

Mary Jane Tunny

Potential Complications of Right Atrial Catheterization

Often credited with the introduction of the use of central venous catheters in humans, 1956 Nobel laureate Werner Forssman stressed acquiring a functional knowledge of anatomy, application of gentle technique, and selection of the proper catheter in order to avoid numerous obvious and potential complications. But even today, almost 30 years later, human error remains the single most frequent cause of complication in the widespread use of central venous catheters.

Richard M. Stillman

Long Term Complications of the Indwelling Central Line Catheters

The ability of providing a route for continuous infusion and the delivery of medications on an outpatient basis has been made possible by the catheters designed by Broviac and Hickman, initially utilized for patients requiring long term parenteral nutrition.(1)

Jose R. Marti

Backmatter

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